MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Medicinal Chemistry' source. Sat, 20 Mar 2010 15:58:20 +0100 http://www.medworm.com/index.php?rid=3360275&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20218964%26dopt%3DAbstract Authors: Gupta SP, Patil VM, Samanta S A k nearest neighbor-molecular field analysis (kNN-MFA) of benzimidazole derivatives, a series of hepatitis C virus (HCV) inhibitors, has been performed to determine the factors contributing the corresponding activities. The energy minimized conformations were obtained by molecular mechanics using VLife QSAR 1.0 package. The developed model was verified by performing leave-one out (LOO) cross-validation, which showed q2 value of 0.900 and pred_r2 value of 0.783. The model indicates the dominance of the steric field and points out the regions around the benzamidazole ring where the bulky or less bulky groups can be substituted to increase the activity of the compounds. PMID: 20218964 [PubMed - as supplied by publisher] (Source: Medicinal Chemis... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=3360275 Thu, 11 Mar 2010 00:00:00 +0100 3360275 http://www.medworm.com/index.php?rid=3360274&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20218965%26dopt%3DAbstract In conclusion, green tea inhibits or delays the deposition of hepatic iron in regularly iron-loaded thalassemic mice effectively. This will prevent the iron-induced generation of free radicals via Haber-Weiss and Fenton reactions, and consequently liver damage and fibrosis. Combined chelation with green tea would be investigated in beta-thalassemia patients with iron overload. PMID: 20218965 [PubMed - as supplied by publisher] (Source: Medicinal Chemistry) Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=3360274 Thu, 11 Mar 2010 00:00:00 +0100 3360274 http://www.medworm.com/index.php?rid=3360270&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20218966%26dopt%3DAbstract Authors: Legoabe LJ, Breytenbach JC, N'da DD, Breytenbach JW The purpose of this study was to synthesize and determine the in vitro transdermal penetration of cytarabine and its 5'-alkyl esters and to establish a correlation, if any, with selected physicochemical properties. The n-alkyl esters were synthesized by acylation of cytarabine (1) at its pharmacophoric 5'-OH. The transdermal flux values of (1) and its esters were determined in vitro using Franz diffusion cell methodology. Aqueous solubility and log D (pH 7.4) values were determined and assessed for correlation to transdermal flux. An inverse relation was observed between the water solubility (Sw) and log D values. Of all esters, (4) exhibited the highest flux value of 22.2 nmol.cm-2.h-1, which is significantly different to th... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=3360270 Thu, 11 Mar 2010 00:00:00 +0100 3360270 http://www.medworm.com/index.php?rid=3360265&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20218967%26dopt%3DAbstract Authors: Thareja S, Aggarwal S, Bhardwaj TR, Kumar M Aldose Reductase (AR), the key enzyme of the polyol pathway catalyzes the reduction of glucose to sorbitol using nicotinamide adenine dinucleotide phosphate as an essential cofactor, has been demonstrated to play an important role in the pathogenesis of diabetic complications. Self Organizing Molecular Field Analysis (SOMFA), a novel three-dimensional quantitative structure activity relationship (3D-QSAR) method has been used in present case to study the correlation between the molecular properties and the aldose reductase inhibitory activities on a series of 5-arylidine-2, 4-thiazolidinedione. SOMFA calculations for both shape and electrostatic potentials were carried out. The master grid maps derived from the best model has been us... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=3360265 Thu, 11 Mar 2010 00:00:00 +0100 3360265 http://www.medworm.com/index.php?rid=3284371&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20158460%26dopt%3DAbstract The objective of this study was to determine the in vitro transdermal permeation through the human stratum corneum (SC) of lamivudine (3TC) (1) and its synthesised methoxypoly(ethylene glycol) (MPEG) carbamates and carbonates thereof in PBS and with the use of Pheroid() as delivery system and to establish a relationship, if any, with selected physicochemical properties. The synthesis and in vitro human skin permeation flux of three N4-methoxypoly(ethylene glycol) carbamates (3)-(5) and three 6'-O-methoxypoly(ethylene glycol) carbonates (6)-(8) of the ARV drug lamivudine are reported. The derivatives were synthesised in a two-step process by coupling activated MPEG oligomers of various chain lengths to either the 4-amino or 6'-hydroxy group of lamivudine. Irrespective of the oligomeric seri... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=3284371 Tue, 16 Feb 2010 00:00:00 +0100 3284371 http://www.medworm.com/index.php?rid=3015578&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19925447%26dopt%3DAbstract Authors: Zheng X, Zhao FF, Liu YM, Yao X, Zheng ZT, Luo X, Liao DF A series of chrysin derivatives were prepared from 2-hydroxyacetophenone, 2,4-dihydroxyacetophenone, 2,4,6-trihydroxy- acetophenone, using modified Baker-Venkataraman transformation. Their anticancer activities in vitro were evaluated by the standard MTT method. The results of biological test showed that some of chrysin derivatives showed stronger anticancer activity than 5-fluorouracil. PMID: 19925447 [PubMed - as supplied by publisher] (Source: Medicinal Chemistry) Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=3015578 Wed, 18 Nov 2009 00:00:00 +0100 3015578 http://www.medworm.com/index.php?rid=3015577&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19925448%26dopt%3DAbstract Authors: Kerth A, Garidel P, Howe J, Alexander C, Mach JP, Waelli T, Blume A, Th Rietschel E, Brandenburg K Lipopolysaccharides (LPS, endotoxins) are main constituents of the outer membranes of Gram-negative bacteria, with the 'endotoxic principle' lipid A anchoring LPS into the membrane. When LPS is removed from the bacteria by the action of the immune system or simply by cell dividing, it may interact strongly with immunocompetent cells such as mononuclear cells. This interaction may lead, depending on the LPS concentration, to beneficial (at low) or pathophysiological (at high concentrations) reactions, the latter frequently causing the septic shock syndrome. There is a variety of endogenous LPS-binding proteins. To this class belong lactoferrin (LF) and hemoglobin (Hb), which have ... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=3015577 Wed, 18 Nov 2009 00:00:00 +0100 3015577 http://www.medworm.com/index.php?rid=2702905&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19673691%26dopt%3DAbstract Authors: Duan Y, Yu J, Liu S, Ji M The synthesis and pharmacological activities of anthraquinone-ibuprofen prodrugs for finding new anti-inflammatory drugs specifically targeting osseous tissues were studied. Two hydrolytically activated anti-inflammatory prodrugs containing anthraquinone moiety and ibuprofen moiety were designed and synthesized. Rhein was chosen as bone-targeting agent and potentially active drug, which was linked chemically with ibuprofen through glycol ester as bone-targeting anti-inflammatory prodrugs. The chemical structures of the new compounds were confirmed by IR, (1)H NMR, (13)C NMR, MS and elemental analysis. The studies of bioactivities demonstrated that both prodrugs showed significant binding capability to hydroxyapatite (HAP), the major component of bone,... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=2702905 Sun, 16 Aug 2009 00:10:17 +0100 2702905 http://www.medworm.com/index.php?rid=2702904&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19673692%26dopt%3DAbstract Authors: Foroumadi A, Sorkhi M, Moshafi MH, Safavi M, Rineh A, Siavoshi F, Shafiee A, Emami S Helicobacter pylori infection is the main cause of gastritis and gastroduodenal ulcer disease, and is associated with gastric cancer. In order to develop new potential anti-Helicobacter pylori candidates, we have investigated the antimicrobial activity of some 2-substituted-5-nitroheterocycles against H. pylori. The anti-Helicobacter pylori activity of selected compounds along with commercially available antibacterial metronidazole was evaluated by comparing the inhibition zone diameters determined using the paper disc diffusion bioassay. The compounds that exhibited strong anti-H. pylori activity at concentration of 8-32 microg/disc (average of inhibition zone >20 mm) were further tested a... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=2702904 Sun, 16 Aug 2009 00:10:14 +0100 2702904 http://www.medworm.com/index.php?rid=2702903&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19673693%26dopt%3DAbstract Authors: Patel A, Karthikeyan C, Moorthy NS, Trivedi P A series of hetaryl imidazoles with VEGF receptors I and II inhibitory activities was subjected to QSAR analysis employing molecular descriptors calculated using QSAR software Dragon. Quantitative models of good statistical significance were formulated for both the activities through stepwise multiple linear regression using the method of least squares and the generated models were evaluated for predictive ability employing cross validation procedure following a leave-one-out scheme. The interpretation of the QSAR models indicated that VEGF receptor II inhibitory activity of the title compounds is influenced by the number of hydrogen acceptor atoms and benzyl groups in the molecule whereas VEGF receptor I inhibitory activity is inf... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=2702903 Sun, 16 Aug 2009 00:10:12 +0100 2702903 http://www.medworm.com/index.php?rid=2702902&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19673694%26dopt%3DAbstract Authors: Saini L, Gupta SP, Kumar Satluri VS A quantitative-structure activity relationship (QSAR) study has been made on two different series of sodium channel blockers - namely, a series of 3-(4-phenoxyphenyl)pyrazoles and a series of 2-alkyl-4-arylimidazoles - and a series of potassium channel blockers that comprises of khellinone derivatives, which act on voltage-gated K(+) channels Kv1.3. In both the cases - the inhibition of Na(+) channels or the inhibition of K(+) channels - the significant correlations were obtained between the inhibition potencies and the hydrophobic properties of the compounds. This led to suggest that the hydrophobic property of the compounds is a major determining factor of the Na(+)/ K(+) channel blocking activity and that the compounds might elicit their ... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=2702902 Sun, 16 Aug 2009 00:10:10 +0100 2702902 http://www.medworm.com/index.php?rid=2702901&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19673695%26dopt%3DAbstract Authors: El-Nezhawy AO, Gaballah ST, Radwan MA, Baiuomy AR, Abdel-Salam OM A series of 2-methyl-N-substituted-benzimidazoles, bearing hydroxypyrrolidinon-5-yl or hydroxypyrrolidin-2-yl, 2,3:5,6-di-O-isopropylidene-alpha-D-mannofuranoside, 2,3,5,6-tetrahydroxy-alpha-D-mannofuranoside, 1:2,5:6-di-O-isopropylidene-alpha-D-gluco-furanose,3-O-benzyl-6,7-dideoxy-1:2-O-isopropylidene-alpha-D-xylo-heptofuranos-5-ulose, 3-O-benzyl-6,7-dideoxy-1,2-dihydroxy-alpha-D-xylo-heptofuranos-5-ulose, 1,2,5,6-tetrahydroxy-alpha-D-glucofuranose sugar moieties, were obtained in good yields from 2-methyl N-(trichloroacetamidomethyl)benzimidazole as a donor and carbohydrate residues as acceptor precursors in the presence of catalytic amount of trimethylsilyl trifluoromethanesulfonate (TMSOTf) as Lewis acid. C... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=2702901 Sun, 16 Aug 2009 00:10:08 +0100 2702901 http://www.medworm.com/index.php?rid=2702900&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19673696%26dopt%3DAbstract The objective of this study was to synthesize derivatives of the anti-HIV drug stavudine (d4T) with more favourable physicochemical properties for transdermal delivery in an effort to increase transdermal penetration of stavudine and thus reduce the severe side effects associated with the dose-dependent oral therapy. The synthesis, hydrolytic stability, and in vitro human skin permeation flux of a series of novel methoxypoly(ethylene glycol) (MPEG) carbonates of stavudine are reported. The carbonates were synthesized in a two-step process by coupling the MPEG promoiety of various chain lengths to C-5' of d4T. In kinetic studies the carbonates proved to be markedly stable in weakly acidic phosphate medium (pH 5.0) with half-lives ranging from 16 to 58 days. The aqueous solubility increased ... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=2702900 Sun, 16 Aug 2009 00:10:05 +0100 2702900 http://www.medworm.com/index.php?rid=2545207&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19534674%26dopt%3DAbstract This study demonstrates that anthraquinone derivatives may be a scaffold to be further developed to obtain selective HIV-1 RNase H inhibitors and represent a new step toward the identification of new anti-RT agents. PMID: 19534674 [PubMed - as supplied by publisher] (Source: Medicinal Chemistry) Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=2545207 Sun, 28 Jun 2009 03:01:31 +0100 2545207 http://www.medworm.com/index.php?rid=2545206&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19534675%26dopt%3DAbstract Authors: Yasmin H, Das S, Nahar L, Masud MM, Rahman MS, Roy SC, Rahman MM, Gibbons S, Kundu JK, Datta BK, Bachar SC, Chowdhury AK, Sarker SD 6-Fluoro-3-oxo-indan-1-acetic acid (5) and 6-fluoroindan-1-acetic acid (6) were conveniently synthesised from 3-fluorobenzaldehyde in four and five steps, respectively. The structures of these new compounds and two other intermediates, 3-fluorobenzylidine-bis-acetoacetate (2) and 3-fluoro-beta-phenyl glutaric acid (3) were elucidated by spectroscopic means, notably, HRMS, 1D and 2D NMR. The analgesic activity of compounds 5 and 6 were assessed by the acetic acid induced writhing in Swiss albino mice. PMID: 19534675 [PubMed - as supplied by publisher] (Source: Medicinal Chemistry) Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=2545206 Sun, 28 Jun 2009 03:01:29 +0100 2545206 http://www.medworm.com/index.php?rid=2545205&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19534676%26dopt%3DAbstract Authors: Vitale G, Corona P, Loriga M, Carta A, Paglietti G, La Colla P, Busonera B, Marongiu E, Collu D, Loddo R In prosecution of an anti-Flaviviridae project a new series of variously substituted 2-diphenyl-benzimidazoles were synthesized and tested in vitro for antiviral and antiproliferative activities. Compounds were tested in cell-based assays against viruses representative of: i) two of the three genera of the Flaviviridae family, i.e. Flaviviruses and Pestiviruses; ii) other RNA virus families, such as Retroviridae, Picornaviridae, Paramyxoviridae, Rhabdoviridae and Reoviridae; iii) two DNA virus families (Herpesviridae and Poxviridae). The 5-Acetyl-2-(4'-nitrobiphenyl-4-yl)-1H-benzimidazole (24) emerged as potent active lead compound against Yellow Fever Virus (a Flavivirus) ... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=2545205 Sun, 28 Jun 2009 03:01:27 +0100 2545205 http://www.medworm.com/index.php?rid=2545204&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19534677%26dopt%3DAbstract Authors: Manivannan , Chaturvedi SC Cyclooxygenase inhibitory and selectivity profile of a combined series of thirty one aryl sulphonamide compounds possessing 4-benzylideneamino or 4-phenyliminomethyl scaffolds were subjected to QSAR study using Hansch approach. The compounds in the selected series were characterized using classical aromatic substituent constants like hydrophobicity (pi), molar refractivity (MR), Hammett electronic (sigma), electronic field effect (F), resonance effect (R), and some indicator variables encoding molecular group contributions. Statistically significant QSAR models were generated using multiple regression analysis and cross-validation tools. The derived QSAR models demonstrated that the COX-2 selectivity over COX-1 is predominantly influenced by the cent... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=2545204 Sun, 28 Jun 2009 03:01:25 +0100 2545204 http://www.medworm.com/index.php?rid=2545203&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19534678%26dopt%3DAbstract Authors: Sriram D, Yogeeswari P, Senthilkumar P, Dewakar S, Rohit N, Debjani B, Bhat P, Veugopal B, Pavan VV, Thimmappa HM Novel 2-[3-(4-bromo-2-fluorobenzyl)-4-oxo-3,4-dihydro-1-phthalazinyl]acetic acid hydrazones were synthesized from phthalic anhydride by a six step synthesis and evaluated for in vitro, in vivo activities against eight mycobacterial species and Mycobacterium tuberculosis (MTB) isocitrate lyase (ICL) enzyme inhibition studies. Among twenty six compounds N'1-[(4-nitrophenyl)methylene]-2-[3-(4-bromo-2-fluorobenzyl)-4-oxo-1,2,3,4-tetrahydro-1-phthalazinyl]ethanohydrazide (7j) was found to be the most active compound in-vitro with MIC's of 0.18 and %lt;0.09 muM against log-phase cultures of MTB and multi-drug resistant MTB respectively. Compound 7j inhibited all the eigh... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=2545203 Sun, 28 Jun 2009 03:01:23 +0100 2545203 http://www.medworm.com/index.php?rid=2545202&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19534679%26dopt%3DAbstract We report in this work the antibacterial evaluation of 12 lipophilic fluoroquinolone derivatives containing diaminoalkyl side chains at C-7 position. The compounds were investigated against 15 bacterial strains including Gram-negative and Gram-positive species of clinical and microbiological importance. Three compounds (5, 10 and 11) were as active as or more efficient than gatifloxacin against Gram-positive bacteria M. lentus. When compared with gatifloxacin compound 10 was 16 times more active. Two compounds (11 and 12) were twice more active than the reference compound against S. aureus. PMID: 19534679 [PubMed - as supplied by publisher] (Source: Medicinal Chemistry) Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=2545202 Sun, 28 Jun 2009 03:01:21 +0100 2545202 http://www.medworm.com/index.php?rid=2545201&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19534680%26dopt%3DAbstract This study assessed the effect of the antidepressants, Fluoxetine and Venlafaxine, on the size (GS), mass (M), cellular volume (CV), of rat parotid salivary glands and salivary flow rate (SFR), as well as the secretagogue action of pilocarpine on this flow. Ninety animals were divided into 9 treatment groups with the antidepressants, antidepressants associated with the application of pilocarpine, antidepressants and physiologic serum, physiologic serum (control) and pilocarpine (positive control). Thirty hours after the end of treatment, saliva collection began, to determine the SFR. Next, the salivary glands were removed, GS and M measured, and the specimens processes for histomorphometric analysis and CV determination. The variable GS presented statistically significant increase among th... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=2545201 Sun, 28 Jun 2009 03:01:19 +0100 2545201 http://www.medworm.com/index.php?rid=2545200&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19534681%26dopt%3DAbstract Authors: Thephinlap C, Phisalaphong C, Fucharoen S, Porter JB, Srichairatanakool S Non-transferrin bound iron (NTBI) is detectable in plasma of %beta;-thalassemia patients and participates in free-radical formation and oxidative tissue damage. Desferrioxamine (DFO), deferiprone (DFP) and deferasirox (DFX) are iron chelators used for treatment of iron overload; however they may cause adverse effects. Curcuminoids (CUR) exhibits many pharmacological activities and presents %beta;-diketone group to bind metal ions. Iron-chelating capacity of CUR was investigated in thalassemic mice. The mice (C57BL/6 stain); wild type (mu%beta;+/+) and heterozygous %beta;-knockout (mu%beta;th-3/+) were fed with ferrocene-supplemented diet for 2 months, and coincidently intervened with CUR (200 mg/kg/day) ... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=2545200 Sun, 28 Jun 2009 03:01:17 +0100 2545200 http://www.medworm.com/index.php?rid=2545199&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19534682%26dopt%3DAbstract Authors: Bhargava D, Karthikeyan C, Moorthy NS, Trivedi P QSAR study was carried out for a series of piperazinyl phenylalanine derivatives exhibiting VLA-4/VCAM-1 inhibitory activity to find out the structural features responsible for the biological activity. The QSAR study was carried out on V-life Molecular Design Suite software and the derived best QSAR model by partial least square (forward) regression method showed 85.67% variation in biological activity. The statistically significant model with high correlation coefficient (r2=0.85) was selected for further study and the resulted validation parameters of the model, crossed squared correlation coefficient (q2=0.76 and pred_r2=0.42) show the model has good predictive ability. The model showed that the parameters SaaNEindex, SsClcou... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=2545199 Sun, 28 Jun 2009 03:01:15 +0100 2545199 http://www.medworm.com/index.php?rid=2545198&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19534683%26dopt%3DAbstract Authors: Naik TR, Naik HS, Naik HR, Bindu PJ, Harish BG, Krishna V The synthesis DNA binding, docking and photoclevage studies of novel benzo[b][1,8]naphthyridines is discribed. The docking studies shows that the derivatives prefers to bind the AT-rich region of double stranded DNA (ds-DNA). The maximum binding energy -7.16 (kcal/mol) was observed for benzo[b][1,8]naphthyridine-5-thiol 5a and it is better candidate as an enantioselective binder to ds-DNA than the other derivatives of benzo[b][1,8]naphthyridines. When photoirradiated at 365 nm, benzo[1,8]-naphthyridines have been found to promote the photocleavage of plasmid pUC19 DNA. PMID: 19534683 [PubMed - as supplied by publisher] (Source: Medicinal Chemistry) Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=2545198 Sun, 28 Jun 2009 03:01:13 +0100 2545198 http://www.medworm.com/index.php?rid=2545196&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19534684%26dopt%3DAbstract Authors: Chuanqiang Q, Shougang G, Hongzhi G, Chunjuan W, Lin M, Yan H, Lei W, Jianwei L, Xingbang W Objectives. To study the mechanisms underlying cerebrogenic multiple organ dysfunction syndrome (CMODS) through investigation of endotoxin levels and the expression of endotoxin receptor CD14 and interleukin IL-1beta mRNAs in a rat CMODS model. Methods. Acute cerebral hemorrhage was induced in Wistar rats by focal intracerebral injection of collagenase into the caudate nucleus. Serum endotoxin levels were quantitated using a chromogenic limulus lysate method; CD14 endotoxin receptor mRNA and IL-1beta mRNA levels in lung and intestine were determined by in situ hybridization. Results. Serum endotoxin levels increased after 12 h, reaching a peak after 24 h, and declined to control levels ... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=2545196 Sun, 28 Jun 2009 03:01:11 +0100 2545196 http://www.medworm.com/index.php?rid=2545194&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19534685%26dopt%3DAbstract Authors: Dell'antone P 3-bromopyruvate (3-BrPA), a pyruvate analog recently proposed as a possible anticancer drug, was investigated in relation to its capacity to inhibit energy production in fractions obtained from normal cells (rat hepatocytes) and in isolated rat thymocytes . Findings were that main targets of the drug were glyceraldehyde 3-phosphate dehydrogenase, and not hexokinase as suggested for hepatoma cells, and succinate -driven ATP synthesis. Consistently with the above findings, in the normal cells studied (thymocytes ) the drug elicited an important fall in ATP levels. The significance of the present findings in concern with a possible therapeutic usefulness of the drug is discussed. PMID: 19534685 [PubMed - as supplied by publisher] (Source: Medicinal Chemistry) Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=2545194 Sun, 28 Jun 2009 03:01:08 +0100 2545194 http://www.medworm.com/index.php?rid=2545192&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19534686%26dopt%3DAbstract Authors: José A, Wolf-Rainer Abraham M Many bacteria grow on surfaces forming biofilms but often high dosages of antibiotics can not clear infectious biofilms. Biofilms are controlled by a process called quorum-sensing triggered by species-specific, small, diffusible autoinducers (N-acyl homoserine lactones (AHL), small peptides or a furanosyl borate diester). Several herbal, animal and microbial extracts possess quorum-quenching activity but only few active compounds and synthetic analogues are known. However, quorum-sensing seems not to be the only way to control biofilms. Bacteria have mechanisms to dissolve their biofilms and return to planktonic lifestyle. Only few compounds responsible for the signalling of these processes are known but may open a completely novel line of bi... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=2545192 Sun, 28 Jun 2009 03:01:06 +0100 2545192 http://www.medworm.com/index.php?rid=2545219&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19442210%26dopt%3DAbstract Authors: Tizot A, Tucker GC, Pierré A, Hickman J, Goldstein S Among the newer and promising weapons against cancer are Farnesyl Transferase Inhibitors (FTI). Indeed it is known that the enzyme Farnesyl Transferase (FT), catalyses the prenylation of cysteine residues of several proteins associated with cancer progression, including oncogenic forms of Ras.FTI could alter tumour progression. Exploration of our corporate structural database, based on concepts of diversity and similarity, brought forward a quinazoline-2,4-dione possessing weak farnesyl transferase inhibitory properties. A systematic modulation of structural parameters allowed the elaboration of a series of analogs out of which the most potent compound (21b) exhibited an IC(50) of 19 nM on FT, an excellent cellular acti... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=2545219 Thu, 30 Apr 2009 23:00:00 +0100 2545219 http://www.medworm.com/index.php?rid=2545218&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19442211%26dopt%3DAbstract Authors: Lajiness J, Sielaff A, Mackay H, Brown T, Kluza J, Nguyen B, Wilson WD, Lee M, Hartley JA Imidazole and pyrrole-containing polyamides belong to an important class of compounds that can be designed to target specific DNA sequences, and they are potentially useful in applications of controlling gene expression. The extent of polyamide curvature is an important consideration when studying the ability of such compounds to bind in the minor groove of DNA. The current study investigates the importance of curvature using polyamides of the form f-Im-Phenyl-Im, in which the imidazole heterocycles are placed in ortho-, meta-, and para-configurations of the phenyl moiety. The synthesis and biophysical evaluation of each compound binding to its cognate DNA sequence (5'-ACGCGT-3') and a ne... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=2545218 Thu, 30 Apr 2009 23:00:00 +0100 2545218 http://www.medworm.com/index.php?rid=2545217&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19442212%26dopt%3DAbstract Authors: Nadkarni DH, Wang F, Wang W, Rayburn ER, Ezell SJ, Murugesan S, Velu SE, Zhang R The high mortality rate and lack of effective therapies make lung cancer an ideal target for novel therapeutic agents. The present study was designed to implement a novel chemical synthesis pathway and to determine the biological activities of synthetic makaluvamine analogs in human lung cancer. Seventeen compounds were synthesized and purified, and their chemical structures were elucidated on the basis of physicochemical constants and NMR spectra. Their in vitro activity was determined in human lung cancer cell lines. Based on initial screens, compound Ic was found to be the most potent, and was therefore used as a model for further studies in lung cancer cells. Ic induced both apoptosis and S-ph... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=2545217 Thu, 30 Apr 2009 23:00:00 +0100 2545217 http://www.medworm.com/index.php?rid=2545216&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19442213%26dopt%3DAbstract Authors: Kalász H, Szöko E, Tábi T, Petroianu GA, Lorke DE, Omar A, Alafifi S, Jasem A, Tekes K After administration of various amounts of pralidoxime to rats, the levels in serum, brain and cerebrospinal fluid (CSF) were measured using capillary zone electrophoresis (CZE). The calibration curves were established using spiked samples. The calibration covers the ranges from 0.3 - 200 microg/mL, 0.3 - 7 microg/mL and 0.1 - 7 microg/mL for serum, brain and CSF, respectively. The CZE measurement opens the way to the fast and reliable determination of pyridinium aldoxime concentrations in serum, cerebrospinal fluid and brain, thereby monitoring blood-brain and blood-CSF penetration of pyridinium aldoxime-type antidotes clinically used in organophosphate poisoning. PMID: 1... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=2545216 Thu, 30 Apr 2009 23:00:00 +0100 2545216 http://www.medworm.com/index.php?rid=2545215&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19442214%26dopt%3DAbstract This study may be used as a guide for mutagenesis studies for designing new inhibitors against H5N1. PMID: 19442214 [PubMed - in process] (Source: Medicinal Chemistry) Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=2545215 Thu, 30 Apr 2009 23:00:00 +0100 2545215 http://www.medworm.com/index.php?rid=2545214&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19442215%26dopt%3DAbstract Authors: Gu RX, Gu H, Xie ZY, Wang JF, Arias HR, Wei DQ, Chou KC Dysfunction in alpha7 nicotinic acetylcholine receptor (nAChR), a member of the Cys-loop ligand-gated ion channel superfamily, is responsible for attentional and cognitive deficits in Alzheimer's disease (AD). To provide useful information for finding drug candidates for the treatment of AD, a study was carried out according to the following procedures. (1) DMXBA, a partial agonist of the alpha7 nAChR, was used as a template molecule. (2) To reduce the number of compounds to be considered, the similarity search and flexible alignment were conducted to exclude those molecules which did not match the template. (3) The molecules thus obtained were docked to alpha7 nAChR. (4) To gain more structural information, the molecular... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=2545214 Thu, 30 Apr 2009 23:00:00 +0100 2545214 http://www.medworm.com/index.php?rid=2545213&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19442216%26dopt%3DAbstract Authors: Wang JF, Yan JY, Wei DQ, Chou KC Cytochrome P450 2C9 (CYP2C9) is an important member of the cytochrome P450 enzyme superfamily with responsibility for metabolizing many important exogenous and endogenous compounds in many species of microorganisms, plants and animals. CYP2C9 is related to the oxidative of 16% of all therapeutics in current clinical use and has adverse drug effects, such as, enzyme induction and inhibition. In order to understand the metabolic mechanism of various drugs, two crystal structures of CYP2C9 have been studied, and their structural differences and structure-activity relationships with the drugs of Fluoxetine, Ibuprofen, Naproxen, Suprofen, and Mefenamic acid were investigated. By a series of docking studies and MD simulations, the binding pockets of ... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=2545213 Thu, 30 Apr 2009 23:00:00 +0100 2545213 http://www.medworm.com/index.php?rid=2545212&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19442217%26dopt%3DAbstract Authors: Agatonovic-Kustrin S, Davies P, Turner JV Antipsychotic medications have a diverse pharmacology with affinity for serotonergic, dopaminergic, adrenergic, histaminergic and cholinergic receptors. Their clinical use now also includes the treatment of mood disorders, thought to be mediated by serotonergic receptor activity. The aim of our study was to characterise the molecular properties of antipsychotic agents, and to develop a model that would indicate molecular specificity for the dopamine (D(2)) receptor and the serotonin (5-HT) transporter. Back-propagation artificial neural networks (ANNs) were trained on a dataset of 47 ligands categorically assigned antidepressant or antipsychotic utility. The structure of each compound was encoded with 63 calculated molecular descriptor... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=2545212 Thu, 30 Apr 2009 23:00:00 +0100 2545212 http://www.medworm.com/index.php?rid=2545211&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19442218%26dopt%3DAbstract Authors: Yuluğ B, Kilic E We have previously shown the neuroprotective effect of atypical antipsychotic agents by experimental cerebral ischemia. However the impact of their high dose related side effects on their low dosage related neuroprotectivity is still unknown.We evaluated the possible neuroprotective effects of high dose olanzapine (10mg/kg) treatment on ischemic brain injury 24 hr after permanent cerebral ischemia. Olanzapine showed neither a neuroprotective nor a neurotoxic effect after focal cerebral ischemia. This finding could suggest that dose related side effect of olanzapine could involve a restriction of its neuroprotective effect unlike lower doses that have been reported to have neuroprotective effect. PMID: 19442218 [PubMed - in process] (Source: Medicinal... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=2545211 Thu, 30 Apr 2009 23:00:00 +0100 2545211 http://www.medworm.com/index.php?rid=2545210&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19442219%26dopt%3DAbstract Authors: Rodríguez Z, López MA, González M, Tolón B, Nadal L, González L, Vélez H, Fini A A series of 3-[(2,5-dihydro-6-hydroxy-2-methyl)-5-oxo-cis-triazin-3-yl]-thiomethyl-cefalosporins with various 3-phenyl-2-propenoyl substituted groups at the 7beta-position were synthesized, structurally characterized and evaluated for antibacterial activity in vitro. To prepare these derivatives by the Vilsmeier's reagent method, it was necessary to carefully control the reaction conditions in order to avoid the formation of the biologically inactive alpha epimer. The NMR studies showed that the 3-phenyl-2-propenoyl moiety has little effect on chemical shifts of cephem nucleus protons and carbon atoms. Some of these cephalosporin derivatives showed good in vitro activ... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=2545210 Thu, 30 Apr 2009 23:00:00 +0100 2545210 http://www.medworm.com/index.php?rid=2545209&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19442220%26dopt%3DAbstract Authors: Samant BS, Sukhthankar MG Febrifugine and its derivatives including halofuginone which possess very high activity against malaria were prepared synthetically from easily available starting material, 3-hydroxy picoline, and using simple reaction conditions. Synthesis of 2-amino-5, 6-methylenedioxy benzoic acid, (which is an intermediate for the process) is described. The selectivity enhancement in nitration of 3, 4-methylenedioxybenzaldehyde towards 6-nitro isomer was done with the help of surfactant. The antimalarial activity of synthesized compounds was determined by using in vitro assays against chloroquine sensitive (D6), chloroquine resistant (W2) Plasmodium falciparum strains for susceptibility and two mammalian cell lines (neuronal cell line NG108 and macrophage cell lin... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=2545209 Thu, 30 Apr 2009 23:00:00 +0100 2545209 http://www.medworm.com/index.php?rid=2545208&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19442221%26dopt%3DAbstract Authors: Jin Z, Zhang WX, Chen B, Mao AW, Cai WM Tacrolimus (FK506) is one of the immunosuppressive drugs used effectively to prevent allograft rejection after liver transplantation. Narrow therapeutic range and individual variance in pharmacokinetics make it difficult to establish a fixed dosage for all patients. Genetic polymorphism in drug metabolizing enzymes and in transporters may influence tacrolimus exposure. A stepwise regression analysis was used to analyze the relationship between blood concentrations of tacrolimus (54 blood samples at the day of 1 week, 2 week and one month after liver transplantation) and genetic & non-genetic factors in 18 Chinese liver transplant patients. The equation of multiple stepwise regression was: Y (tacrolimus' blood concentration) = 34.534 ... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=2545208 Thu, 30 Apr 2009 23:00:00 +0100 2545208 http://www.medworm.com/index.php?rid=2256885&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275709%26dopt%3DAbstract Authors: Bekhit AA, Ashour HM, Bekhit Ael-D, Bekhit SA The synthesis of novel series of structurally related 4-pyrazolyl benzenesulfonamide derivatives is described. All the newly synthesized compounds were examined for their anti-inflammatory activity using cotton pellet induced granuloma and carrageenan induced rat paw edema bioassays. In addition the inhibitory activities of cyclooxygenase-1 and cyclooxygenase-2 (COX-1 and COX-2), ulcerogenic effect and acute toxicity were determined. Furthermore, all the compounds were evaluated for their in vitro antimicrobial activity against Eischerichia coli, Staphylococcus aureus and Candida albicans. Docking poses for compounds 6b and 7b separately in the active site of the human COX-2 enzyme and DNA-gyrase B were also obtained. The results r... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=2256885 Sun, 01 Mar 2009 05:00:00 +0100 2256885 http://www.medworm.com/index.php?rid=2256884&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275710%26dopt%3DAbstract Authors: Kumar P, Emami S, Kresolek Z, Yang J, McEwan AJ, Wiebe LI (18)F-Labelled fluoroazomycin arabinoside ([(18)F]FAZA) is a 2-nitroimidazole (azomycin) based PET tracer used extensively in cancer clinics to diagnose tumour hypoxia. The hypoxia-specific uptake and rapid blood clearance kinetics of FAZA contribute to good tumor-to-background ratios (T/B ratios) and high image contrast. However, FAZA, an alpha-configuration nucleoside, is not transported by cellular nucleoside transporters. It enters cells only via diffusion, therefore not achieving the high uptake and T/B ratios characteristic of actively transported radiopharmaceuticals. The present work describes the synthesis, physicochemical properties and preliminary assessment of the radiosensitization properties of two novel a... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=2256884 Sun, 01 Mar 2009 05:00:00 +0100 2256884 http://www.medworm.com/index.php?rid=2256883&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275711%26dopt%3DAbstract Authors: Balaji S, Chempakam B Cheminformatics approaches are currently not employed in any of the spices to study the medicinal properties traditionally attributed to them. The aim of this study is to find the most efficacious molecule which do not have toxic effects but at the same time have desired pharmacokinetic profile. In the present study of the class 'diphenylheptanoids' from turmeric, cheminformatics methods were employed to predict properties such as physicochemical properties, Absorption, Distribution, Metabolism, Toxicity (mutagenicity, rodent carcinogenicity and human hepatotoxicity). These studies confirmed that curcumin and its derivatives cause dose-dependent hepatotoxicity. The results of these studies indicate that, in contrast to curcumin, few other compounds in tur... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=2256883 Sun, 01 Mar 2009 05:00:00 +0100 2256883 http://www.medworm.com/index.php?rid=2256882&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275712%26dopt%3DAbstract Authors: Kusirisin W, Srichairatanakool S, Lerttrakarnnon P, Lailerd N, Suttajit M, Jaikang C, Chaiyasut C Ethanolic extracts of 30 Thai medicinal plants, traditionally used as alternative treatments in diabetes, were evaluated for antioxidative activity by the 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) method. They were evaluated in vitro for oxidative stress by thiobarbituric acid-reactive substance (TBARS) assay in pooled plasma of diabetic patients compared to without treatment of the extracts (control). The extracts were also assayed for protein glycation. The results showed that five plants had strong antioxidant activity: Phyllanthus emblica Linn. (PE), Terminalia chebula Retz. (TC), Morinda citrifolia Linn. (MC), Kaempferia parviflora Wall. (K... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=2256882 Sun, 01 Mar 2009 05:00:00 +0100 2256882 http://www.medworm.com/index.php?rid=2256881&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275713%26dopt%3DAbstract Authors: Naik HR, Naik HS, Naik TR, Bindu PJ, Naika HR, Aravinda T, Lamani DS The use of nanostructured TiO(2) as mixed phase photocatalyst in the synthesis of 2H-pyrano/2H-thiopyrano [2,3-b]quinoline-2-carboxylic acid (2a/2b) is described. The binding modes of 2a/2b with ds DNA fragments d(CGCGAATTCGCG) were predicted by molecular docking studies. The lowest energy was found in the compound 2b with a binding energy of -7.44 Kcal/mol and inhibition constant of 5.39 x e(-6). The interaction study with CT DNA was carried out by absorption spectra, (K(b) constant obtained for 2a is 3.5x10(6) and for 2b it is 2.9x10(5)), viscosity and thermal denaturation methods. The in vitro antioxidant activities were evaluated. Finally, the results showed that the intercalated 2a/2b compounds are stron... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=2256881 Sun, 01 Mar 2009 05:00:00 +0100 2256881 http://www.medworm.com/index.php?rid=2256880&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275714%26dopt%3DAbstract Authors: Malovichko OL, Krysko AA, Kabanova TA, Andronati SA, Grishkovets VI, Kachala VV, Panov DA It has been proposed a novel method for obtaining of 1,2,3,4-tetrahydroisoquinoline-7-carboxylic acid as Arg-mimetic within the framework of search for novel fibrinogen receptor antagonists. New alpha (IIb)beta(3) antagonists were prepared on a base of 1,2,3,4-tetrahydroisoquinoline-7-carboxylic acid. Their high antiaggregatory activities in a human platelet rich plasma and ability to block FITC-Fg binding to alpha (IIb)beta(3) on washed human platelets were estimated. PMID: 19275714 [PubMed - in process] (Source: Medicinal Chemistry) Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=2256880 Sun, 01 Mar 2009 05:00:00 +0100 2256880 http://www.medworm.com/index.php?rid=2256879&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275715%26dopt%3DAbstract Authors: Capasso A The effect exerted by two gamma-endorphin derivatives (DTgammaE and DEgammaE) was investigated on morphine-induced inhibition on the electrically induced contractions of guinea pig ileum in vitro. Morphine (1x10(-8)-5x10 (-8)-1x10 (-7) M) dose dependently and significantly reduced the E.C. of guinea pig ileum, IC50=6.5x10(-8) M (Confidence limits: 3.7x10 (-8)-9.1x10 (-8)). DTgammaE and DEgammaE per se (1x10 (-6)-5x10 (-6)-1x10 (-5) M) did not modify significantly the E.C. of guinea pig ileum. Furthermore, DTgammaE or DEgammaE injection 10-30-60 min before morphine, did not affect the inhibitory effect of morphine on the E.C. of guinea pig ileum. By contrast, ilea from guinea-pigs treated for 4 days with DTgammaE or DEgammaE (1 mg/Kg/i.p.) were less sensitive to the i... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=2256879 Sun, 01 Mar 2009 05:00:00 +0100 2256879 http://www.medworm.com/index.php?rid=2256878&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275716%26dopt%3DAbstract We report here synthesis and evaluation of radiopharmaceuticals based on the second-generation MDR-reversing drug MS-209. 5-[3-{4-(2-Phenyl-2-(4'-[(125)I]iodo-phenyl)acetyl)piperazin-1-yl}-2-hydroxypropoxy]quino-line (17) was prepared from the 4'-tributylstannyl precursor (16) in >95% radiochemical yield. (16) was synthesized in a six-step process with the overall yield of 25%. In vitro studies were conducted in MES-SA (drug-sensitive) and MES-SA/Dx5 (MDR) human uterine sarcoma cell lines. In vivo studies were performed in athymic mice bearing MES-SA and MES-SA/Dx5 xenografts. The uptake of (17) is higher in MES-SA than MES-SA/Dx5 cells. The uptake and efflux of (17) depend on temperature and concentration, and indicate active transport mechanism(s). Incubation of drug sensitive MES-SA ... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=2256878 Sun, 01 Mar 2009 05:00:00 +0100 2256878 http://www.medworm.com/index.php?rid=2256877&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275717%26dopt%3DAbstract Authors: Bourdron J, Barbier P, Allegro D, Villard C, Lafitte D, Commeiras L, Parrain JL, Peyrot V The most widely used molecules in cancer chemotherapy are Vinca-alkaloids and Taxoids, numerous chemists attempted the synthesis of analogs which bind to their well-known tubulin pharmacological site. Unfortunately, tumors develop resistance to these compounds; therefore the definition of anchoring points and potential binding sites for new drugs on tubulin is of major interest. Caulerpenyne (Cyn), the major secondary metabolite synthesized by the green marine alga Caulerpa taxifolia could be one of these drugs, since it inhibits the assembly of tubulin and MTP (Barbier et al., 2001). We observed that the tubulin-Cyn complex is poorly reversed. Cyn did not bind to sulfhydryl groups and th... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=2256877 Sun, 01 Mar 2009 05:00:00 +0100 2256877 http://www.medworm.com/index.php?rid=2256876&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275718%26dopt%3DAbstract Authors: Ochiuz L, Peris JE Microparticles of chitosan (CHT) containing alendronate sodium (AL) were prepared in four drug:polymer ratios (1:1, 1:2, 1:4, 1:6) using the spray drying technique. The efficiency of the method was evaluated by determining production yield (about 70 %) and microencapsulation efficiency, which was almost 100 % in the case of all four of the formulations studied. Particles had a mean size of between 3.6 and 4.6 mum, and a near-spherical shape. The formulations with the highest content of AL (drug:polymer ratio 1:1 and 1:2) showed an asymmetrical distribution of particles, which were larger in size, and had a higher proportion of irregular particles than the other formulations. FT-IR analysis revealed an ionic interaction between AL and CHT. Differential scanni... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=2256876 Sun, 01 Mar 2009 05:00:00 +0100 2256876 http://www.medworm.com/index.php?rid=2256875&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275719%26dopt%3DAbstract Authors: Kurosu M, Crick DC Potent inhibitors of MenA (1,4-dihydroxy-2-naphtoate prenyltrasferase) in Mycobacterium tuberculosis are identified, and are also effective in inhibiting growth of Mycobacterium tuberculosis at low concentrations. The MenA inhibitors possess common chemical structural features of (alkylamino)oalkoxyphenyl)(phenyl)methanones. Significantly, the MenA inhibitors can be synthesized in a few steps with high overall yields. The representative MenA inhibitors are highly effective in killing nonreplicating Mycobacterium tuberculosis that is evaluated by using the Wayne low oxygen model. In addition, a series of drug resistant Mycobacterium spp. are sensitive to the MenA inhibitors. The results are expected to be of significance in terms of discovering new lead compo... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=2256875 Sun, 01 Mar 2009 05:00:00 +0100 2256875 http://www.medworm.com/index.php?rid=2145177&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19149646%26dopt%3DAbstract Authors: Li S, Chiu G, Pulito VL, Liu J, Connolly PJ, Middleton SA An alpha 1a- and alpha 1d-adrenergic receptor (AR) selective antagonist may be a more efficacious treatment for BPH/LUTS patients and may have fewer side effects than the existing pharmaceuticals. A facile synthesis for a series of (2-cyclopropoxyphenyl)piperidine derivatives has been developed, in which aryl vinyl ether formation and subsequent cyclopropyl formation provide efficient access to key intermediate N-Boc-4-(2-cyclopropoxyphenyl)piperidine. The synthesized (2-cyclopropoxyphenyl)piperidine derivatives display high affinity and selectivity for alpha1a-AR and alpha1d-AR compared to alpha1b-AR and D2 receptor, Ki values for alpha1a-AR are 0.91 nM to 79.0 nM and alpha1d-AR are 2.0 nM to 57 nM; Ki values for alpha... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=2145177 Thu, 01 Jan 2009 05:00:00 +0100 2145177 http://www.medworm.com/index.php?rid=2117049&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19149644%26dopt%3DAbstract Authors: Capasso A Recently, we have demonstrated that substitution of 1,2,3,4 tetrahyidroisoquinoline-3- carboxylic acid (Tic) in place of Gly2 in dynorphin A-(1-13)-NH2 (DYN) analogue (A) decreased the affinity to the kappa, delta, and mu receptors, and kappa selectivity. The doubly substituted analogue [2',6'-dimethyl-L-tyrosine (Dmt1)-Tic2]DYN (B) exhibited high delta-affinity (Ki=0.39 nM) while mu- and kappa-affinities were only an order of magnitude less (4-5 nM). Bioactivity of [Tic2]DYN peptide (A) on guinea-pig ileum and rabbit jejunum revealed potent delta- and kappa-antagonism thus indicating that the conversion from a kappa-agonist to antagonist occurred with the inclusion of Tic into DYN analogues, similar to the appearance of antagonist properties with delta-opioid agonis... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=2117049 Thu, 01 Jan 2009 05:00:00 +0100 2117049 http://www.medworm.com/index.php?rid=2117048&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19149645%26dopt%3DAbstract Exploring the Relationship of Drug-Induced Neutrophil Immaturity & Haematological Toxicity to Drug Chemistry Using Quantitative Structure-Activity Models. Med Chem. 2009 Jan;5(1):7-14 Authors: Delieu JM, Horobin RW, Duguid JK An investigation of the relationships between physicochemical features of ten antipsychotic drugs and previously reported influence of these drugs on neutrophil maturity was made. A quantitative structure-activity relations (QSAR) approach was adopted, in which several numerical parameters describing physicochemical characteristics of the antipsychotics were estimated. Possible connections between these parameters and neutrophil maturity were explored. Influence of drug physicochemistry on the incidence of agranulocytosis and neutropenia reported in th... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=2117048 Thu, 01 Jan 2009 05:00:00 +0100 2117048 http://www.medworm.com/index.php?rid=2117047&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19149646%26dopt%3DAbstract Authors: Li S, Chiu G, Pulito VL, Liu J, Connolly PJ, Middleton SA An alpha (1a)- and alpha (1d)-adrenergic receptor (AR) selective antagonist may be a more efficacious treatment for BPH/LUTS patients and may have fewer side effects than the existing pharmaceuticals. A facile synthesis for a series of (2-cyclopropoxyphenyl)piperidine derivatives has been developed, in which aryl vinyl ether formation and subsequent cyclopropyl formation provide efficient access to key intermediate N-Boc-4-(2-cyclopropoxyphenyl)piperidine. The synthesized (2-cyclopropoxyphenyl)piperidine derivatives display high affinity and selectivity for alpha(1a)-AR and alpha(1d)-AR compared to alpha(1b)-AR and D(2) receptor, K(i) values for alpha(1a)-AR are 0.91 nM to 79.0 nM and alpha(1d)-AR are 2.0 nM to 57 nM; K... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=2117047 Thu, 01 Jan 2009 05:00:00 +0100 2117047 http://www.medworm.com/index.php?rid=2117046&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19149647%26dopt%3DAbstract Authors: Liedtke RK The causes of increased rates of myocardial infarctions and strokes by application of non-steroidal anti-inflammatory agents (NSAIDs) are unclear. Here we present a biochemical model that the long-term vascular effects of NSAIDs can be consequences of their antiproliferative cellular mechanism. The analysis of the model suggests that the intramitochondrial uncoupling of oxidative phosphorylation induced by NSAIDs increases, through a reduced activity of ATP-dependent ionic pumps, the intra-cellular calcium x phosphate product with a consecutively increased formation and export of various calcium phosphate compounds. The latter cause, by chemical replication mechanisms of arterial hydroxyapatite deposits, a metatstatic calcifying vascular process. This sclerogenic va... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=2117046 Thu, 01 Jan 2009 05:00:00 +0100 2117046 http://www.medworm.com/index.php?rid=2117045&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19149648%26dopt%3DAbstract Authors: Liu GT Chronic viral hepatitis B and C are diseases worldwide. At present, the number of effective and safe drugs for treatment of HBV and HCV is still limited. In order to develop novel anti-viral hepatitis drug, a number of analogues of the active component schizandrin C from Fructus Schiznadrae, a Chinese herb used in the therapy of viral hepatitis, were synthesized. Bicyclol, one of the analogues, was demonstrated to have actions of anti-hepatitis virus replication in duck hepatitis model and 2.2.15 cell line, anti-experimental liver injury induced by hepatotoxins such as CCl(4), acetaminophen and ConA, and anti-liver fibrosis in rats and mice. The active mechanism of bicyclol might be anti-apoptosis of hepatocytes through multiple signaling pathways mainly inducing the ex... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=2117045 Thu, 01 Jan 2009 05:00:00 +0100 2117045 http://www.medworm.com/index.php?rid=2117044&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19149649%26dopt%3DAbstract In conclusion, the results show the ability of MS to modify skeletal muscle response to mepivacaine. PMID: 19149649 [PubMed - as supplied by publisher] (Source: Medicinal Chemistry) Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=2117044 Thu, 01 Jan 2009 05:00:00 +0100 2117044 http://www.medworm.com/index.php?rid=2117043&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19149650%26dopt%3DAbstract Authors: Zaheer-Ul-Haq , Iqbal S Among neutral endopeptidase (NEP) inhibitors, mercaptoacyldipeptides implicated in cardiovascular diseases, are of great interest. Two groups, Coric et al. and Oefner et al. described two different binding preferences for mercaptoacyldipeptides at the active site of NEP. By focusing on both, 3D-QSAR studies were performed on mercaptoacyldipeptides, based on conformational alignment obtained by GOLD 3.2, using CoMFA and CoMSIA techniques. Statistically significant 3D-QSAR models were obtained with q(2) of 0.580 and 0.559, and r(2) of 0.996 and 0.991, respectively. Both the models were validated by an external test set of nine compounds giving highly predictive r(2)((pred)) of 0.929 and 0.928, respectively. The study will facilitate the rational design of... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=2117043 Thu, 01 Jan 2009 05:00:00 +0100 2117043 http://www.medworm.com/index.php?rid=2117042&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19149651%26dopt%3DAbstract Authors: Borchhardt DM, Andricopulo AD Three-dimensional quantitative structure-activity relationships (3D-QSAR) were performed for a series of analgesic cyclic imides using the CoMFA and CoMSIA methods. Significant correlation coefficients (CoMFA, r(2) = 0.95 and q(2) = 0.72; CoMSIA, r(2) = 0.96 and q(2) = 0.76) were obtained, and the generated models were externally validated using test sets. The final QSAR models as well as the information gathered from 3D contour maps should be useful for the design of novel cyclic imides having improved analgesic activity. PMID: 19149651 [PubMed - as supplied by publisher] (Source: Medicinal Chemistry) Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=2117042 Thu, 01 Jan 2009 05:00:00 +0100 2117042 http://www.medworm.com/index.php?rid=2117041&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19149652%26dopt%3DAbstract This study aimed to measure salivary flow rate of rats under chronic treatment with benzodiazepine (Diazepam((R))), to analyze by histomorphometry the effects of the drug in the parotids glands and to verify the effect of the pilocarpine in glandular parenchyma and in the salivary flow rate. Seventy-two male Wistar rats were allocated to four groups. Control groups received saline during 60 days (C60) and pilocarpine (Pilo) during 60 days. Experimental groups were dealt with Diazepam((R)) associated with saline (DS), and Diazepam((R)) associated with pilocarpine (DP) during 60 days. The stimulated salivary flow rate was obtained by using the gravimetric method. After the animals were killed, parotid glands were removed and mass and size were determined. The specimens were processed and ste... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=2117041 Thu, 01 Jan 2009 05:00:00 +0100 2117041 http://www.medworm.com/index.php?rid=2117040&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19149653%26dopt%3DAbstract Authors: Bitencourt M, Freitas MP The activities of a series of benzothiazole derivatives, some Candida albicans N-myristoyltransferase (Nmt) inhibitors, were modeled through MIA-QSAR (multivariate image analysis applied to quantitative structure-activity relationship) by using two different regression methods: N-PLS, applied to the three-way array, and PLS, applied to the unfolded array. Both models demonstrated excellent predictive ability, with results comparable to those obtained through 3D approaches. In order to compare the results obtained through MIA descriptors with the predictions of a classical 2D QSAR, some representative physicochemical descriptors were calculated and regressed against the experimental pIC(50) values through multiple linear regression, demonstrating that M... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=2117040 Thu, 01 Jan 2009 05:00:00 +0100 2117040 http://www.medworm.com/index.php?rid=2117039&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19149654%26dopt%3DAbstract Authors: Satuluri VS, Seelam J, Gupta SP There has been an increasing interest in compounds that modulate potassium ion channels (K(+)-channels) since they can be developed as important therapeutic agents against ischemic heart diseases. Of the diverse family of K(+)-channels, the voltage-gated potassium channel Kv1.3 constitutes an attractive target for the selective suppression of effector memory T cells in autoimmune diseases. For the development of antiarrythmic drugs, the blockade of the rapidly activating delayed rectifier (I(Kr)) and slowly activating delayed rectifier (I(Ks)) potassium currents has been specifically studied. Since the discovery of I(Ks)-channel, its blockers have been particularly more studied. In this communication, we present QSAR studies on a few series of K... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=2117039 Thu, 01 Jan 2009 05:00:00 +0100 2117039 http://www.medworm.com/index.php?rid=2117038&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19149655%26dopt%3DAbstract Authors: Sturzu A, Klose U, Echner H, Regenbogen M, Kalbacher H, Gharabaghi A, Heckl S Peptide conjugates derived from the SV 40 T antigen nuclear localisation sequence (NLS) have been successfully used to translocate both fluorescein isothiocyanate (FITC) and Gadolinium (Gd)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) into the cytoplasm and nucleus of glioma cells. However, uptake occurred only in up to 35% of cells. To improve cellular uptake, we designed three novel FITC-labelled Gd-DOTA conjugates. In the first conjugate, the commonly used Gd-DOTA-complex was coupled to the nuclear localization sequence (NLS) of the Simian Virus (SV) 40 T antigen alone as a control. In the second conjugate, the Gd-DOTA-coupled SV 40 T antigen NLS was elongated by the HIV-1 tat p... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=2117038 Thu, 01 Jan 2009 05:00:00 +0100 2117038 http://www.medworm.com/index.php?rid=2041679&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18991736%26dopt%3DAbstract Authors: Saitoh T, Yamashita A, Abe K, Ogawa K, Kitabatake M, Taguchi K, Horiguchi Y The chemical structure of selegiline, a commercially available drug for Parkinson's disease (PD), resembles that of 1,2,3,4-tetrahydroisoquinoline (TIQ), an endogenous parkinsonism-inducing compound. In the present study, we evaluated the direct cytotoxicity of (R)- and (S)-3-methyl-TIQ (3-MeTIQ) and (R)- and (S)-3-methyl-N-propargyl-TIQ (3-Me-N-propargyl-TIQ), as selegiline-mimetic TIQ derivatives, and their ability to prevent 1-methyl-4-phenylpyridinium iodide (MPP(+))-induced cell death. Synthesis of optically-pure 3-MeTIQs was achieved via the super acid-induced cyclization of chiral N-benzyl-N-[1-methyl-2-(phenylsulfinyl)ethyl]formamide using a Pummerer-type cyclization reaction as the key step in... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=2041679 Sat, 01 Nov 2008 04:00:00 +0100 2041679 http://www.medworm.com/index.php?rid=2041678&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18991746%26dopt%3DAbstract Authors: Vitale G, Carta A, Loriga M, Paglietti G, La Colla P, Busonera B, Collu D, Loddo R Being involved in an anti-Flaviviridae Project, and because of the role played by benzimidazole derivatives as promising inhibitors of the HCV helicase and RNA polymerase, as well as of the Zn finger transcription factor, we synthesized a new series of 2-arylbenzimidazoles and evaluated them for antiviral activity, as well as for antiproliferative activity. Compounds were tested in cell-based assays against viruses representative of: i) two of the three genera of the Flaviviridae family, i.e. Flaviviruses and Pestiviruses; ii) other RNA virus families, such as Retroviridae, Picornaviridae, Paramyxoviridae, Rhabdoviridae and Reoviridae; iii) two DNA virus families (Herpesviridae and Poxviridae). ... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=2041678 Sat, 01 Nov 2008 04:00:00 +0100 2041678 http://www.medworm.com/index.php?rid=1956092&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18991733%26dopt%3DAbstract Authors: Howe J, Richter W, Hawkins L, Rössle M, Alexander C, Fournier K, Mach JP, Waelli T, Gorczynski RM, Ulmer AJ, Brade H, Zamyatina A, Kosma P, Th Rietschel E, Brandenburg K Although hemoglobin (Hb) is mainly present in the cytoplasm of erythrocytes (red blood cells), lower concentrations of pure, cell-free Hb are released permanently into the circulation due to an inherent intravascular hemolytic disruption of erythrocytes. Previously it was shown that the interaction of Hb with bacterial endotoxins (lipopolysaccharides, LPS) results in a significant increase of the biological activity of LPS. There is clear evidence that the enhancement of the biological activity of LPS by Hb is connected with a disaggregation of LPS. From these findings one questions whether the property t... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1956092 Sat, 01 Nov 2008 04:00:00 +0100 1956092 http://www.medworm.com/index.php?rid=1956091&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18991734%26dopt%3DAbstract Authors: Bongiovanni M, Casana M Non-invasive markers of liver fibrosis have been recently developed as a possible alternative to liver biopsy. The clinical management of hepatic diseases is dependent on the extent of liver fibrosis. Liver biopsy remains the gold standard but severe complications are found in about 0.5% of cases. Studies involving sequential liver biopsies are impractical, costly, and risky. Therefore non-invasive markers of liver fibrosis could be useful. These drawbacks justify an intensive research on non-invasive alternatives. Several serum markers are either directly involved in fibrosis remodelling or are indirectly associated with the presence of significant liver fibrosis. More recently, fibrosis scores calculated from statistical models have been described. Th... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1956091 Sat, 01 Nov 2008 04:00:00 +0100 1956091 http://www.medworm.com/index.php?rid=1956090&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18991735%26dopt%3DAbstract Authors: Fiore G, Capasso A Preeclampsia (PE) is a multisystem disorder that remains a major cause of maternal and foetal morbidity and death. To date, no treatment has been found that prevents the development of the disease. Endothelial dysfunction is considered to underlie its clinical manifestations, such as maternal hypertension, proteinuria and edema; and oxidative stress has been increasingly postulated as a major contributor to endothelial dysfunction in PE. A large body of research has investigated the potential role of antioxidant nutrients in the prevention of PE in women at high increased risk of the disease. Therefore, the present study was primarly designed to assess the potential benefit of antioxidant supplementation on markers of placental oxidative stress in an in vitr... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1956090 Sat, 01 Nov 2008 04:00:00 +0100 1956090 http://www.medworm.com/index.php?rid=1956089&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18991736%26dopt%3DAbstract Authors: Saitoh T, Yamashita A, Abe K, Ogawa K, Kitabatake M, Taguchi K, Horiguchi Y The chemical structure of selegiline, a commercially available drug for Parkinson's disease (PD), resembles that of 1,2,3,4-tetrahydroisoquinoline (TIQ), an endogenous parkinsonism-inducing compound. In the present study, we evaluated the direct cytotoxicity of (R)- and (S)-3-methyl-TIQ (3-MeTIQ) and (R)- and (S)-3-methyl-N-propargyl-TIQ (3-Me-N-propargyl-TIQ), as selegiline-mimetic TIQ derivatives, and their ability to prevent 1-methyl-4-phenylpyridinium iodide (MPP(+))-induced cell death. Synthesis of optically-pure 3-MeTIQs was achieved via the super acid-induced cyclization of chiral N-benzyl-N-[1-methyl-2-(phenylsulfinyl)ethyl]formamide using a Pummerer-type cyclization reaction as the key step in... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1956089 Sat, 01 Nov 2008 04:00:00 +0100 1956089 http://www.medworm.com/index.php?rid=1956088&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18991737%26dopt%3DAbstract Authors: Akhtar T, Hameed S, Khan KM, Choudhary MI Chiral 3-substituted-4-amino-5-thioxo-1H,4H-1,2,4-triazoles (5a-i) were synthesized. The target molecules were prepared by cyclization of the corresponding dithiocarbazinic acids, obtained from hydrazides, in the presence of hydrazine hydrate. The chiral hydrazides were in turn synthesized form L-amino acids. The structures of all the compounds were confirmed by modern spectroscopic techniques and purity ascertained by elemental analysis. The synthesized compounds 5a-i were evaluated for urease inhibition and found to exhibit varying degrees of urease inhibition activity showing IC(50) values ranging from 22.0 +/- 0.5 to 43.8 +/- 0.3 microM. Compound 5b was found to be the most active, exhibiting IC(50) = 22.0 +/- 0.5 microM comparable... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1956088 Sat, 01 Nov 2008 04:00:00 +0100 1956088 http://www.medworm.com/index.php?rid=1956087&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18991738%26dopt%3DAbstract Authors: Ouguerram K, Zair Y, Billon S, Chétiveaux M, Brunet-François C, Ngohou-Bach K, Allavena C, Reliquet V, Milpied B, Magot T, Raffi F, Krempf M The aim was to study the mechanisms involved in the dyslipidemia associated with lipodystrophy in HIV infected patients on antiretroviral therapy (ART). We investigated the in vivo kinetics of apolipoprotein B100 (apoB) containing lipoproteins using a 14 h primed constant infusion of [5,5,5, (2)H(3)] leucine and compartmental modelling in normolipidemic without lipodystrophy (7 patients, NLD) or dyslipidemic with lipodystrophy (7 patients, LD) treated with ART. Subjects in group LD showed higher plasma triglycerides (5.73+/-3.58 vs 1.29+/-0.54 g/L, p<0.005), total cholesterol (2.98+/-0.95 vs 1.74+/-0.26 g/L, p<0.05), apoB ... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1956087 Sat, 01 Nov 2008 04:00:00 +0100 1956087 http://www.medworm.com/index.php?rid=1956086&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18991739%26dopt%3DAbstract Authors: Pizzimenti S, Barrera G, Calzavara E, Mirandola L, Toaldo C, Dianzani MU, Comi P, Chiaramonte R The role of the Notch1 pathway has been well assessed in leukemia. Notch1 mutations are the most common ones in T acute lymphoblastic leukaemia patients which carry either oncogenic Notch1 forms or ineffective ubiquitin ligase implicated in Notch1 turnover. Abnormalities in the Notch1-Jagged1 system have been reported also in acute myelogenous leukaemia (AML) patients where Jagged1 is frequently over-expressed. Moreover, activating Notch1 mutations, as well, can occur in human AML and in leukemia cases with lineage infidelity. As a result, Notch1 signalling inhibition is an attractive goal in leukaemia therapy. Blockage/delay in cell differentiation and/or increase of proliferation ... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1956086 Sat, 01 Nov 2008 04:00:00 +0100 1956086 http://www.medworm.com/index.php?rid=1956085&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18991740%26dopt%3DAbstract Authors: Romagnoli R, Baraldi PG, Sarkar T, Cara CL, Lopez OC, Carrion MD, Preti D, Tolomeo M, Balzarini J, Hamel E Microtubules are among the most successful targets for development of compounds useful for anticancer therapy. Continuing our project to develop new small molecule antitumor agents, two new series of derivatives based on the 2-aroyl-4-phenylbenzofuran molecular skeleton were synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymerization and cell cycle effects. SAR were elucidated with various substitutions on the benzoyl moiety at the 2-position of the benzofuran ring. The most promising compound in this series, the (5-hydroxy-4-phenylbenzofuran-2-yl)(4-methoxyphenyl)methanone derivative (3d), has significant growth inhibitory activity in t... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1956085 Sat, 01 Nov 2008 04:00:00 +0100 1956085 http://www.medworm.com/index.php?rid=1956084&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18991741%26dopt%3DAbstract Authors: Leung JC, Ragland N, Marphis T, Silverstein DM The NMDA receptor (NMDAR) is expressed in the renal proximal tubule. NMDAR agonists and antagonists induce cell toxicity in the central nervous system (CNS). We studied the effect of NMDAR agonists and antagonists on renal cell survival in renal culture cells: proximal tubule-like opossum kidney (OK) and distal-tubule-like madine darby canine kidney cells (MDCK) cells. Low dose glutamate had no effect on cell survival. However, 10 mM glutamate induced a 14-fold increase in cell death compared to control cells. Addition of low or high doses of the NMDAR agonist glycine had no effect on cell toxicity. Exposure of cells to the non-competitive NMDAR blocker MK-801 or the competitive NMDAR antagonist CPP induced a time and dose-depende... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1956084 Sat, 01 Nov 2008 04:00:00 +0100 1956084 http://www.medworm.com/index.php?rid=1956083&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18991742%26dopt%3DAbstract In this study, we administered hemin (ferriprotoporphyrin chloride, 30 micromol/kg b.w., subcutaneously), a potent inducer of HO-1, every 3 days to rats following subcutaneous administration of MCT (60 mg/kg) and examined its effect on MCT-induced PH and pulmonary inflammation. MCT administration caused pulmonary arterial wall thickening with marked elevation of right ventricular pressure, in association with prominent pulmonary inflammation as revealed by the increase in gene expression of tumor necrosis factor-alpha and the number of infiltrated neutrophils in the lung. In contrast, hemin treatment of MCT-administered animals, which led to a further increase in pulmonary HO-1 mRNA expression, significantly ameliorated MCT-induced PH as well as tissue inflammation. These findings suggest ... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1956083 Sat, 01 Nov 2008 04:00:00 +0100 1956083 http://www.medworm.com/index.php?rid=1956082&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18991743%26dopt%3DAbstract Authors: Kumar A, Saxena JK, Chauhan PM A novel series of 4-amino-5-cyano-2, 6-disubstituted pyrimidines have been synthesized and evaluated for their in vitro antifilarial DNA topoisomerase II activity against filarial parasite Setaria Cervi. In particular compounds bearing 4-chloro-phenyl substitutent at position-6, exhibited strong inhibition at 40 microg/mL and 5 microg/mL concentration. The present study based on the biological results obtained, suggests that the nature of substitutent at position-4 in the phenyl ring directly affects DNA topoisomerase II inhibitory activity. Most of the compounds have shown better topoisomerase II inhibitory activity than the standard antifilarial drug (DEC) and the topoisomerase II inhibitors (Novobiocin, Nalidixic acid). PMID: 18991743 [Pub... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1956082 Sat, 01 Nov 2008 04:00:00 +0100 1956082 http://www.medworm.com/index.php?rid=1956081&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18991744%26dopt%3DAbstract Authors: Maria K, Dimitra HL, Maria G Chalcones and Mannich bases have been reported to present antiinflammatory activities as well as inhibitory activities on several factors implicated in inflammation disorders. A series of chalcones and some related Mannich bases were prepared by Claisen-Schmidt condensation of appropriate acetophenones with appropriate aromatic aldehyde. Mannich bases were derived from chalcones, with formaldehyde and the corresponding amine. The compounds were tested in vitro for their ability to inhibit various enzymes involved in the arachidonic acid cascade, for their antioxidant behaviour and in vivo for anti-inflammatory activity. Some chalcones and Mannich bases present strong anti-inflammatory and antioxidant activities. Almost all the tested compounds pres... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1956081 Sat, 01 Nov 2008 04:00:00 +0100 1956081 http://www.medworm.com/index.php?rid=1956080&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18991745%26dopt%3DAbstract Authors: Fu J, Meng X, He J, Gu J p38 MAPK has been the key therapeutic target for multiple inflammation diseases. However, the clinical applications of p38 inhibitors, most of which target on the ATP binding groove in the kinase, have been held back, largely because of their limited specificity and severe side-effects. An alternative strategy to generate highly selective p38 inhibitor is to block the specific interaction in the p38 signal pathway. Based on the hypothesis that specific binding peptides targeting on the docking groove would interfere the intrinsic interaction between p38 and its partners, we have designed a fusion peptide containing 12aa p38 docking sequence derived from MKK3b and 11aa HIV-TAT transmembrane sequence to form a cell permeable peptide. The peptide specific... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1956080 Sat, 01 Nov 2008 04:00:00 +0100 1956080 http://www.medworm.com/index.php?rid=1956079&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18991746%26dopt%3DAbstract Authors: Vitale G, Carta A, Loriga M, Paglietti G, La Colla P, Busonera B, Collu D, Loddo R Being involved in an anti-Flaviviridae Project, and because of the role played by benzimidazole derivatives as promising inhibitors of the HCV helicase and RNA polymerase, as well as of the Zn finger transcription factor, we synthesized a new series of 2-arylbenzimidazoles and evaluated them for antiviral activity, as well as for antiproliferative activity. Compounds were tested in cell-based assays against viruses representative of: i) two of the three genera of the Flaviviridae family, i.e. Flaviviruses and Pestiviruses; ii) other RNA virus families, such as Retroviridae, Picornaviridae, Paramyxoviridae, Rhabdoviridae and Reoviridae; iii) two DNA virus families (Herpesviridae and Poxviridae). ... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1956079 Sat, 01 Nov 2008 04:00:00 +0100 1956079 http://www.medworm.com/index.php?rid=1956078&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18991747%26dopt%3DAbstract This study provides basis for the evaluation of sesquiterpenoids as alternative or possible synergistic compounds for current antimicrobial chemotherapeutics, showing the practical utility of natural derived products to increase the susceptibility of E. coli and S. aureus. PMID: 18991747 [PubMed - in process] (Source: Medicinal Chemistry) Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1956078 Sat, 01 Nov 2008 04:00:00 +0100 1956078 http://www.medworm.com/index.php?rid=1956077&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18991748%26dopt%3DAbstract Authors: Gorczynski R, Boudakov I, Khatri I Our laboratory and others have documented in some detail the immunological consequences which follow from interaction of the ubiquitously expressed molecule CD200 with its receptor(s) CD200R (expressed predominantly on cells of myeloid and lymphoid origin). In particular, there is evidence that these interactions lead to immunosuppressive signals which modulate graft rejection responses; decrease the manifestations of arthritis in rodent models; diminish mast cell mediator release in models of allergic disease; and favour the growth of tumors in both mice and humans. The development of small molecular weight agonists (and/or antagonists) of these interactions would thus likely have significant clinical importance. The data reported herein cha... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1956077 Sat, 01 Nov 2008 04:00:00 +0100 1956077 http://www.medworm.com/index.php?rid=1795283&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18782042%26dopt%3DAbstract Authors: Mayur YC, Ahmad O, Prasad VV, Purohit MN, Srinivasulu N, Kumar SM A series of N10-substituted-2-methyl acridone derivatives are synthesized and are examined for its ability to reverse P-glycoprotein (P-gp) mediated multidrug resistance (MDR) in breast cancer cell lines MCF-7 and MCF-7/Adr. The structural requirement of in-vitro anti-cancer and reversal of drug resistance are studied. The results showed that compound 16 with four carbon spacer exhibited promising in-vitro anti-cancer and reversal of drug resistance in comparison to the other analogues. PMID: 18782042 [PubMed - in process] (Source: Medicinal Chemistry) Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1795283 Mon, 01 Sep 2008 04:00:00 +0100 1795283 http://www.medworm.com/index.php?rid=1795282&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18782048%26dopt%3DAbstract Authors: Ghosh P, Pal A, Shavrin A, Bornmann W, Gelovani JG, Alauddi MM N3-Substitued thymidine analogues that carry a carboranylalkyl moiety at the N3-position with various spacer lengths have been reported to be good substrates for thymidine kinase (TK1). As part of our continuing effort towards the development of new TK1 substrates for imaging tumor proliferative activity, we have synthesized a series of new N3-substituted analogues of thymidine that carry an aromatic ring with different spacer lengths. The overall yields for 6 and 7 were 13% and 39% in four steps and three steps, respectively, and those for 14, 16 and 18 were in the range of 13%-15% in six steps. The overall yield for 24 was 33% in three steps, and those for 25 and 26 were 64% and 58%, respectively, in one step. Mo... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1795282 Mon, 01 Sep 2008 04:00:00 +0100 1795282 http://www.medworm.com/index.php?rid=1783606&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18782038%26dopt%3DAbstract Authors: Paunescu E, Susplugas S, Boll E, Varga RA, Mouray E, Grellier P, Melnyk P Amodiaquine remains one of the most prescribed antimalarial 4-aminoquinoline. To assess the importance of the 4'-hydroxyl group and subsequent hydrogen bond in the antimalarial activity of amodiaquine (AQ), a series of new analogues in which this functionality was replaced by various amino groups was synthesized. The incorporation of a 3'-pyrrolidinamino group instead of the 3'-diethylamino function of AQ allowed the development of a parallel series of amopyroquine derivatives. The compounds were screened against both chloroquine (CQ)-sensitive and -resistant strains of Plasmodium falciparum and their cytotoxicity evaluated upon the MRC5 cell line. Antimalarial activity in a low nanomolar range was recor... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1783606 Mon, 01 Sep 2008 04:00:00 +0100 1783606 http://www.medworm.com/index.php?rid=1783605&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18782039%26dopt%3DAbstract Authors: Henry M, Alibert S, Baragatti M, Mosnier J, Baret E, Amalvict R, Legrand E, Fusai T, Barbe J, Rogier C, Pagès JM, Pradines B The capacity of ten molecules for reversing resistance in Plasmodium falciparum in vitro to quinoline antimalarial drugs, such as chloroquine (CQ), quinine (QN), mefloquine (MQ) and monodesethylamodiaquine (MDAQ), was assessed against 27 Plasmodium falciparum isolates. Four of these compounds were 9,10-dihydroethanoanthracene derivatives (DEAs). These DEAs reversed 75 to 92% of the CQ resistant strains. These synthetic compounds were more effective in combination with CQ than verapamil, ketotifen, chlorpromazine, reserpine or nicardipine, which reversed less than 50% of the CQ resistant strains. DEAs significantly reversed 67 to 100% of MDAQ resista... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1783605 Mon, 01 Sep 2008 04:00:00 +0100 1783605 http://www.medworm.com/index.php?rid=1783604&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18782040%26dopt%3DAbstract Authors: Kgokong JL, Matsabisa GM, Smithand PP, Breytenbach JC A series of N,N-bis(trifluoromethylquinolin-4-yl)- and N,N-bis[2,8-bis(trifluoromethyl)quinolin-4-yl] diamino alkane and piperazine derivatives were synthesised by employing a simple and rapid displacement reaction of the 4-chloro group on the 2-trifluoromethyl- and 2,8-bis(trifluoromethyl)-quinoline by diaminoalkane or piperazine groups. Results of in vitro antimalarial activity evaluations of these compounds against the chloroquine-sensitive (D10) and chloroquine-resistant (K1) strains of Plasmodium falciparum indicate that compounds with trifluoromethyl groups in both the 2 and 8 positions coupled with diaminoalkyl bridging chains of 2 to 6 carbon atoms exhibit a slightly higher activity than compound with only a trifluo... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1783604 Mon, 01 Sep 2008 04:00:00 +0100 1783604 http://www.medworm.com/index.php?rid=1783603&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18782041%26dopt%3DAbstract Authors: Solomon VR, Haq W, Smilkstein M, Srivastava K, Rajakumar S, Puri SK, Katti SB Malaria is one of the foremost public health problems in developing countries affecting nearly 40% of the global population. Apart from this, the past two decade's emergence of drug resistance has severely limited the choice of available antimalarial drugs. Furthermore, the general trend emerging from the SAR-studies is that chloroquine resistance does not involve any change to the target of this class of drugs but involves compound specific efflux mechanism. Based on this premise a number of groups have developed short chain analogues of 4-aminoquinoline, which are active against CQ-resistant strains of P. falciparum in in vitro studies. However, these derivatives undergo biotransformation (de-alkly... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1783603 Mon, 01 Sep 2008 04:00:00 +0100 1783603 http://www.medworm.com/index.php?rid=1783602&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18782042%26dopt%3DAbstract Authors: Mayur YC, Ahmad O, Prasad VV, Purohit MN, Srinivasulu N, Kumar SM A series of N(10)-substituted-2-methyl acridone derivatives are synthesized and are examined for its ability to reverse P-glycoprotein (P-gp) mediated multidrug resistance (MDR) in breast cancer cell lines MCF-7 and MCF-7/Adr. The structural requirement of in-vitro anti-cancer and reversal of drug resistance are studied. The results showed that compound 16 with four carbon spacer exhibited promising in-vitro anti-cancer and reversal of drug resistance in comparison to the other analogues. PMID: 18782042 [PubMed - in process] (Source: Medicinal Chemistry) Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1783602 Mon, 01 Sep 2008 04:00:00 +0100 1783602 http://www.medworm.com/index.php?rid=1783601&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18782043%26dopt%3DAbstract Authors: Kumar CS, Chandru H, Sharada AC, Thimmegowda NR, Prasad SB, Kumar MK, Rangappa KS A series of novel 1-benzhydryl-sulfonyl-piperazine derivatives 3(a-e) were synthesized by nucleophilic substitution reaction of 1-benzhydryl-piperazine with different sulfonyl chlorides and were characterized by (1)H NMR, LC/MS, FTIR and elemental analysis. In the present study, the compounds 3(a-e) exhibited in vivo inhibition of Ehrlich ascites tumor (EAT) cell growth and increased the Median Survival Time (MST) and %ILS of EAT bearing mice. Further treatment of derivatives in vivo resulted in reduction of EAT cell number and ascites formation. The efficacy of the derivatives to inhibit the angiogenesis in vivo was evaluated in tumor bearing mice peritoneum and chorio allantoic membrane (CAM) m... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1783601 Mon, 01 Sep 2008 04:00:00 +0100 1783601 http://www.medworm.com/index.php?rid=1783600&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18782044%26dopt%3DAbstract In conclusion, DBM mediates the induction of phase II enzymes by Nrf2 activation and inhibits benzo[a]pyrene induced DNA adducts by enhancing its detoxification in lungs. PMID: 18782044 [PubMed - in process] (Source: Medicinal Chemistry) Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1783600 Mon, 01 Sep 2008 04:00:00 +0100 1783600 http://www.medworm.com/index.php?rid=1783599&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18782045%26dopt%3DAbstract Authors: Dinakaran M, Senthilkumar P, Yogeeswari P, China A, Nagaraja V, Sriram D Thirty four novel 7-fluoro/nitro-1,2-dihydro-5-oxo-8-(sub)-5H-thiazolo[3,2-a]quinoline-4-carboxylic acids were synthesized from 2,4-dichlorobenzoic acid and 2,4-dichloro-5-fluoroacetophenone by multi step reaction, evaluated for in vitro and in vivo antimycobacterial activities against Mycobacterium tuberculosis H37Rv (MTB), multi-drug resistant Mycobacterium tuberculosis (MDR-TB) and Mycobacterium smegmatis (MC(2)) and also tested for the ability to inhibit the supercoiling activity of DNA gyrase from M. smegmatis. Among the synthesized compounds, 8-[6-[[(1,1-dimethylethoxy)carbonyl]amino]-3-azabicyclo[3.1.0]hex-3-yl]-1,2-dihydro-7-nitro-5-oxo-5H-thiazolo[3,2-a]quinoline-4-carboxylic acid (10q) was found... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1783599 Mon, 01 Sep 2008 04:00:00 +0100 1783599 http://www.medworm.com/index.php?rid=1783598&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18782046%26dopt%3DAbstract The objective of our study is to generate new leads through different mode of action and to optimize their structure to display the potent efficacy. PMID: 18782046 [PubMed - in process] (Source: Medicinal Chemistry) Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1783598 Mon, 01 Sep 2008 04:00:00 +0100 1783598 http://www.medworm.com/index.php?rid=1783597&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18782047%26dopt%3DAbstract Authors: Foroumadi A, Safavi M, Emami S, Siavoshi F, Najjari S, Safari F, Shafiee A Helicobacter pylori is now recognized as the primary etiological factor associated with gastritis, peptic ulcer disease and gastric cancers. Fluoroquinolones have been shown to be active against H. pylori. For develop new anti-H. pylori agents, we have investigated the SAR of a series of N-(phenethyl)piperazinyl quinolones for their antimicrobial activity against H. pylori. The anti-H. pylori activity of synthesized compounds along with commercially available anti-H. pylori agents such as metronidazole, and parent quinolones was evaluated by the disc diffusion bioassay. The results indicated that the potency and anti-H. pylori activity profile of the quinolones is highly dependent on the type of substit... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1783597 Mon, 01 Sep 2008 04:00:00 +0100 1783597 http://www.medworm.com/index.php?rid=1783596&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18782048%26dopt%3DAbstract Authors: Ghosh P, Pal A, Shavrin A, Bornmann W, Gelovani JG, Alauddi MM N(3)-Substitued thymidine analogues that carry a carboranylalkyl moiety at the N(3)-position with various spacer lengths have been reported to be good substrates for thymidine kinase (TK1). As part of our continuing effort towards the development of new TK1 substrates for imaging tumor proliferative activity, we have synthesized a series of new N(3)-substituted analogues of thymidine that carry an aromatic ring with different spacer lengths. The overall yields for 6 and 7 were 13% and 39% in four steps and three steps, respectively, and those for 14, 16 and 18 were in the range of 13%-15% in six steps. The overall yield for 24 was 33% in three steps, and those for 25 and 26 were 64% and 58%, respectively, in one st... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1783596 Mon, 01 Sep 2008 04:00:00 +0100 1783596 http://www.medworm.com/index.php?rid=1680356&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18673140%26dopt%3DAbstract In this study, disubstituted benzohydroxamic acid, benzaldoximes and dihalosalicylic acid dimers were synthesized and tested as inhibitors of [(125)I]ET-1 binding to ET(A) receptors in rat embryonic cardiomyocyte (H9c2 cell) membranes. Some dihalosalicylic acid dimers 2h showed good inhibitory activity, the most active compounds are the hydroxamic acids derived from anthranilic acid. Among these compounds, the 3, 5-diiodo-2-aminobenzohydroxamic acid e compound 2a is three-folds more potent as inhibitor of [(125I)] ET-1 binding to ET(A) receptors than the 3; 5-diiodosalicylic acid reported in literature. Most aryl aldoximes in this study were biologically inactive as inhibitors of [(125I)] ET-1 binding to ET(A) receptors. PMID: 18673140 [PubMed - in process] (Source: Medicinal Chemistry... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1680356 Tue, 01 Jul 2008 04:00:00 +0100 1680356 http://www.medworm.com/index.php?rid=1680355&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18673141%26dopt%3DAbstract Authors: Capasso A Dependence can be induced and measured in vitro by using guinea-pig ileum. Tissues from untreated animals, after a brief exposure to opioids, show a strong naloxone-induced contracture indicating that the cellular mechanisms of dependence may occur very rapidly following occupation of receptors and that these mechanisms operate within the myenteric plexus. The characteristics of dependence development and the precipitation of withdrawal by naloxone in the guinea-pig ileum are very similar to those of acute dependence in experimental animals and man. Several observations support the hypothesis that brain serotoninergic system has been widely implicated in many of the pharmacological effects of opioids. Manipulations that alter the activity of serotonin in the central ... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1680355 Tue, 01 Jul 2008 04:00:00 +0100 1680355 http://www.medworm.com/index.php?rid=1680354&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18673142%26dopt%3DAbstract Authors: Dessalew N, Singh SK Cyclin dependent kinase 2 (CDK2) has appeared as an important drug target over the years with a multitude of therapeutic potentials. With the intention of designing compounds with enhanced inhibitory potencies against CDK2, the 3D-QSAR CoMFA and CoMSIA study on benzodipyrazoles series is presented here. The developed models showed a strong correlative and predictive capability having a cross validated correlation co-efficient of (r(2)(cv)) 0.699 for CoMFA and 0.794 for CoMSIA models. A very good conventional and predicted correlation co-efficients were also obtained: CoMFA (r(2)(ncv), r(2)(pred): 0.883, 0.754), CoMSIA (0.937, 0.815). The models were found to be statistically robust and are expected to be of an aid to design and/or prioritize drug likes for... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1680354 Tue, 01 Jul 2008 04:00:00 +0100 1680354 http://www.medworm.com/index.php?rid=1680353&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18673143%26dopt%3DAbstract Authors: Izuhara K, Kanaji S, Arima K, Ohta S, Shiraishi H IL-4 and IL-13, two related Th2-type cytokines, play critical and redundant roles in the defense against gastrointestinal nematodes. These cytokines exert various immunological and physiological effects to expel these worms; however, it had not been known whether protease/protease inhibitor interaction was involved in the defense mechanism against these parasites. Many protozoan and helminth parasites generate cysteine proteases, the majority of which are orthlogues of mammalian cathepsin L, and these cysteine proteases play key roles in the life cycle of parasites as they infect and/or adapt to the hosts. We previously found that the squamous cell carcinoma antigens (SCCA1) and SCCA2, members of the ovalbumin serpin family, we... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1680353 Tue, 01 Jul 2008 04:00:00 +0100 1680353 http://www.medworm.com/index.php?rid=1680352&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18673144%26dopt%3DAbstract Authors: Weber KC, Honório KM, Andricopulo AD, Da Silva AB 5-HT(1A) receptor plays an important role in the delayed onset of antidepressant action of a class of selective serotonin reuptake inhibitors. Moreover, 5-HT(1A) receptor levels have been shown to be altered in patients suffering from major depression. In this work, hologram quantitative structure-activity relationship (HQSAR) studies were performed on a series of arylpiperazine compounds presenting affinity to the 5-HT(1A) receptor. The models were constructed with a training set of 70 compounds. The most significant HQSAR model (q(2) = 0.81, r(2) = 0.96) was generated using atoms, bonds, connections, chirality, and donor and acceptor as fragment distinction, with fragment size of 6-9. Predictions for an external test set... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1680352 Tue, 01 Jul 2008 04:00:00 +0100 1680352 http://www.medworm.com/index.php?rid=1680351&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18673145%26dopt%3DAbstract Authors: García MJ, Martínez-Martos JM, Mayas MD, Carrera MP, De la Chica S, Cortés P, Ramírez-Expósito MJ The hypothalamus-pituitary-adrenal axis (HPA) participates in the maintenance of cardiovascular functions and in the control of blood pressure. By other hand, it is known that blood pressure regulation and HPA activity are affected by sex hormones. The aim of the present work is to analyze the influence of estradiol and progesterone on renin-angiotensin system (RAS)-regulating aminopeptidase A, aminopeptidase B and aminopeptidase N activities and vasopressin-degrading activity in the HPA axis of ovariectomized mice and ovariectomized mice treated subscutaneously with different doses of estradiol and progesterone. Our data suggest that in female mice, estra... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1680351 Tue, 01 Jul 2008 04:00:00 +0100 1680351 http://www.medworm.com/index.php?rid=1680350&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18673146%26dopt%3DAbstract Authors: Heckl S, Sturzu A, Regenbogen M, Beck A, Feil G, Gharabaghi A, Echner H The seven N-terminal amino acids AVPIAQK (SmacN7) of the mitochondrial protein Smac (second mitochondria-derived activator of caspase) promote caspase activation by binding specifically to inhibitor of apoptosis proteins (IAPs) and blocking their inhibitory activity. SmacN7 cannot pass through the cell membrane, but to be of therapeutic use it would be essential for it to enter the cell. To achieve transmembrane transport of SmacN7 we coupled it to a novel fluorescein isothiocyanate (FITC)-labelled transmembrane transport peptide RRRRK(FITC)RRRR via ss-alanine to produce the conjugate AVPIAQKssA RRRRK(FITC)RRRR. Because IAPs are much more strongly expressed in the cytoplasm of tumor cells, we expected this... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1680350 Tue, 01 Jul 2008 04:00:00 +0100 1680350 http://www.medworm.com/index.php?rid=1680349&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18673147%26dopt%3DAbstract Authors: Sersen F, Loos D, Mezesová L, Lácová M Flavonoids, which generally exhibit very good antioxidant properties, contain the chromone unity. The work elucidates the relation between chemical structure of chromones and their ability to scavenge DPPH radicals. The work deals with antioxidative properties of some hydroxy derivatives of 3-formylchromones (without substituent, 6-hydroxy-, 7-hydroxy-, 7,8-dihydroxy-). It was found that the last two derivatives scavenge DPPH radicals, whereas the first two ones do not. It was demonstrated that the presence and location of hydroxyl groups play a crucial role for antioxidative activity of 3-formylchromones. The scavenging of DPPH radicals runs through H(+) abstraction from hydroxyl groups of formylchromones. The DPPH scaveng... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1680349 Tue, 01 Jul 2008 04:00:00 +0100 1680349 http://www.medworm.com/index.php?rid=1680348&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18673148%26dopt%3DAbstract This study analyzed the effect of metformin on oxidative stress markers (thiobarbituric acid reactive substances (TBARS), malondialdehyde (MDA) and carbonyl groups), hydrogen peroxide (H(2)O(2)) levels, non-enzymatic antioxidant defenses [reduced (GSH) and oxidized (GSSG) glutathione and vitamin E] and enzymatic antioxidant defenses [glutathione peroxidase (GPx), glutathione reductase (GRed) and manganese superoxide dismutase (MnSOD)] in brain homogenates of diabetic GK rats, a model of type 2 diabetes. For this purpose we compared brain homogenates obtained from untreated GK rats versus GK rats treated with metformin during a period of 4 weeks. Brain homogenates obtained from Wistar rats were used as control. The MDA levels, GPx and GRed activities are significantly higher in untreated GK... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1680348 Tue, 01 Jul 2008 04:00:00 +0100 1680348 http://www.medworm.com/index.php?rid=1680347&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18673149%26dopt%3DAbstract Authors: Ounjaijean S, Thephinlap C, Khansuwan U, Phisalapong C, Fucharoen S, Porter JB, Srichairatanakool S Plasma non-transferrin bound iron (NTBI) is potentially toxic and contributes to the generation of reactive oxygen species (ROS), consequently leading to tissue damage and organ dysfunction. Iron chelators and antioxidants are used for treatment of thalassemia patients. Green tea (GT) contains catechins derivatives that have many biological activities. The purpose of this study was to investigate the iron-chelating and free-radical scavenging capacities of green tea extract in vivo. Rats were injected ip with ferric citrate together with orally administered GT extract (GTE) for 4 months. Blood was collected monthly for measurement of iron overload and oxidative stress indicators... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1680347 Tue, 01 Jul 2008 04:00:00 +0100 1680347 http://www.medworm.com/index.php?rid=1680346&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18673150%26dopt%3DAbstract Authors: Kostova I, Traykova M, Rastogi VK The cerium (III), lanthanum (III) and neodymium (III) complexes of 5-aminoorotic acid were synthesized and their structures were determined by means of theoretical study, spectral and physicochemical analysis. Significant differences in the spectra of the complexes were observed as compared to the spectra of the ligand. The ligand and the complexes were tested for the antioxidant activity. The results obtained indicate that the tested compounds exerted a considerable antioxidant effect upon the evaluated radicals' formation in the blood plasma of Wistar rat. PMID: 18673150 [PubMed - in process] (Source: Medicinal Chemistry) Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1680346 Tue, 01 Jul 2008 04:00:00 +0100 1680346 http://www.medworm.com/index.php?rid=1680345&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18673151%26dopt%3DAbstract Authors: Sutherland GR, Tyson RL, Auer RN There is a misconception that hypoglycemic nerve cell death occurs easily, and can happen in the absence of coma. In fact, coma is the prerequisite for neuronal death, which occurs via metabolic excitatory amino acid release. The focus on nerve cell death does not explain how most brain neurons and all glia survive. Brain metabolism was interrogated in rats during and following recovery from 40 min of profound hypoglycemia using ex vivo (1)H MR spectroscopy to determine alterations accounting for survival of brain tissue. As previously shown, a time-dependent increase in aspartate was equaled by a reciprocal decrease in glutamate/glutamine. We here show that the kinetics of aspartate formation during the first 30 min (0.36 +/- 0.03 micromol g(-... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1680345 Tue, 01 Jul 2008 04:00:00 +0100 1680345 http://www.medworm.com/index.php?rid=1680344&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18673152%26dopt%3DAbstract Authors: Asai D, Kodama KB, Shoji Y, Nakashima H, Kawamura K, Oishi J, Kuramoto M, Niidome T, Katayama Y Gene therapy is a growing topic in the medical arena. Since the safety system of gene therapy has not been sufficiently established, its clinical use is limited. Recently, we developed a cell-specific gene regulation system based on a new concept, D-RECS, or Drug and Gene Delivery System Responding to Cellular Signals. We hoped here to apply this D-RECS concept to gene therapy for virus infections. In the present study, we report the design, synthesis and characterization of the functional polymers, which are able to discriminate normal and human immunodeficiency virus type 1 (HIV-1) infected cells. In the D-RECS concept, certainafety system of gene therapy has not been sufficiently... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1680344 Tue, 01 Jul 2008 04:00:00 +0100 1680344 http://www.medworm.com/index.php?rid=1680343&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18673153%26dopt%3DAbstract Authors: Harpstrite SE, Collins SD, Oksman A, Goldberg DE, Sharma V Emergence of chloroquine (CQ) resistant Plasmodium falciparum strains necessitates discovery of inexpensive antimalarial drugs capable of targeting CQ-resistant strains. Towards this objective, herein we have synthesized and characterized naphthalene-Schiff bases or naphthalene-amine phenols. Among these compounds, 7 demonstrated a significant bioactivity with a half-maximal inhibitory concentration (IC(50)) of 1.7 microM against CQ-resistant Dd2 strains. PMID: 18673153 [PubMed - in process] (Source: Medicinal Chemistry) Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1680343 Tue, 01 Jul 2008 04:00:00 +0100 1680343 http://www.medworm.com/index.php?rid=1680342&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18673154%26dopt%3DAbstract Authors: Leong MK, Chen TH An in silico model for predicting human cytochrome P450 2B6-substrate interactions was generated based on a novel scheme, which was initially devised to predict the hERG liability (reported in Leong, M. K., Chem. Res. Toxicol., 2007, 20, 217.) using pharmacophore ensemble/support vector machine to take into account the protein conformational flexibility while interacting with structurally diverse substrates. This is of critical importance yet never being addressed by any analogue-based molecular modeling studies before. Thirty-seven molecules were chosen from the literature and scrutinized for structural integrity and data consistency, of which 26 were treated as the training set to generate models, which were subject to validation by the other 11 molecules a... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1680342 Tue, 01 Jul 2008 04:00:00 +0100 1680342 http://www.medworm.com/index.php?rid=1632555&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18473916%26dopt%3DAbstract Authors: Rajwade RP, Pande R, Mishra KP, Kumar A, Pandey BN Hydroxamic acids the multifunctional molecules with general formula R'-C(=O)NROH have interesting medicinal and biological potentiality. The antiproliferative activity of 12 hydroxamic acids has been tested in vitro towards human adenocarcinama cell line by MTT assay. The IC(50) values were found to be in the range from 12 to 152.8microM. The most potent product identified is N-p-chlorophenyl-4-nitrobenzohydroxamic acid with IC(50) value 12microM. The RP-HPLC experiment of these molecules was performed with 50:50(V)/(V) % methanol - water mixture as mobile phase. A QSAR is developed for the human adenocarcinoma cells inhibitory activity of a series of hydroxamic acids (n=1-12) that are structurally related to hydroxyurea. Mult... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1632555 Thu, 01 May 2008 04:00:00 +0100 1632555 http://www.medworm.com/index.php?rid=1567222&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18473911%26dopt%3DAbstract Authors: Carta A, Piras S, Paglietti G, Pricl S, La Colla P, Busonera B, Loddo R A series of quinoxalines variously substituted, namely 3-arylthiomethyl-1,6-dimethylquinoxalin-2-ones (6a-f), 3-arylthiomethyl-1-benzyl-7-trifluoromethylquinoxalin-2-ones (8a-g) and 2-arylthiomethyl-3-benzyloxy-6-trifluoro-methylquinoxalines (10a,b,e-h), were synthesized and compared with previous arylphenoxymethylquinoxalines (1a-f, 2a-f and 3a-b). The purpose was to verify whether the replacement of oxygen with sulphur atom and the insertion of different substituents on the phenyl side chain were able to improve the capability to inhibit the Pgp pump and restore the antiproliferative activity of clinically useful drugs, such as doxorubicin (Doxo), vincristine (VCR) and etoposide (VP16), in drug-resistant... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1567222 Thu, 01 May 2008 04:00:00 +0100 1567222 http://www.medworm.com/index.php?rid=1567221&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18473912%26dopt%3DAbstract Authors: Zhang J, Xu W, Liu A, Du G A series of pyrrolidine derivatives were designed and synthesized in good yields starting from commercially available 4-hydroxy-L-proline using a suitable synthetic strategy. And their ability to inhibit neuraminidase was evaluated. These compounds showed potent inhibitory activity against influenza A (H3N2) neuraminidase. Within this series, four compounds, 6e, 9c, 9f and 10e, have the good potency (IC(50)=1.56 approximately 2.40microM) which is compared to the NA inhibitor oseltamivir (IC(50)=1.06microM), and could be used as lead compound in the future. PMID: 18473912 [PubMed - in process] (Source: Medicinal Chemistry) Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1567221 Thu, 01 May 2008 04:00:00 +0100 1567221 http://www.medworm.com/index.php?rid=1567220&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18473913%26dopt%3DAbstract Authors: Canduri F, Perez PC, Caceres RA, de Azevedo WF The family of Cyclin-Dependent Kinases (CDKs) can be subdivided into two major functional groups based on their roles in cell cycle and/or transcriptional control. CDK9 is the catalytic subunit of positive transcription elongation factor b (P-TEFb). CDK9 is the kinase of the TAK complex (Tat-associated kinase complex), and binds to Tat protein of HIV, suggesting a possible role for CDK9 in AIDS progression. CDK9 complexed with its regulatory partner cyclin T1, serves as a cellular mediator of the transactivation function of the HIV Tat protein. P-TEFb is responsible for the phosphorylation of the carboxyl-terminal domain of RNA Pol II, resulting in stimulation of transcription. Furthermore, the complexes containing CDK9 induce the... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1567220 Thu, 01 May 2008 04:00:00 +0100 1567220 http://www.medworm.com/index.php?rid=1567219&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18473914%26dopt%3DAbstract In this study, we present data showing that the aqueous extract of Arbutus unedo's leaves exerts inhibitory action on interferon-gamma (IFN-gamma) elicited activation of STAT1, both in human breast cancer cell line MDA-MB-231 and in human fibroblasts. This down-regulation of STAT1 is shown to result from a reduced tyrosine phosphorylation of STAT1 protein. Evidence is also presented indicating that the inhibitory effect of this extract may be mediated through enhancement of tyrosine phosphorylation of SHP2 tyrosine phosphatase. The modulation of this nuclear factor turns out into the regulation of the expression of a number of genes involved in the inflammatory response such as inducible nitric oxide synthase (iNOS) and intercellular adhesion molecule-1 (ICAM-1). Taken together, our result... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1567219 Thu, 01 May 2008 04:00:00 +0100 1567219 http://www.medworm.com/index.php?rid=1567218&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18473915%26dopt%3DAbstract Synthesis, evaluation and QSAR studies of 16-(4 & 3,4-substituted) benzylidene androstene derivatives as anticancer agents. Med Chem. 2008 May;4(3):229-36 Authors: Dubey S, Kaur P, Jindal DP, Satyanarayan YD, Piplani P In a systematic effort aimed at identifying new steroidal cytotoxic agents with potent antipoliferative activity against cancer cells and developing their QSAR models, series of 4-nitro, 4-isopropyl, 4-methoxy and 3,4-dimethoxy substituted benzylidene androst-5-ene derivatives were synthesized. The selected compounds were evaluated for antineoplastic activity against a panel of three human cell lines-breast, CNS and lungs at NCI, Bethesda, USA. The results presented herein reports that compounds 7, 9, 10, 15,16, 18, 20-25, 30, 32-36 and 44 have been found to ... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1567218 Thu, 01 May 2008 04:00:00 +0100 1567218 http://www.medworm.com/index.php?rid=1567217&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18473916%26dopt%3DAbstract Authors: Rajwade RP, Pande R, Mishra KP, Kumar A, Pandey BN Hydroxamic acids the multifunctional molecules with general formula R'-C(=O)NROH have interesting medicinal and biological potentiality. The antiproliferative activity of 12 hydroxamic acids has been tested in vitro towards human adenocarcinama cell line by MTT assay. The IC(50) values were found to be in the range from 12 to 152.8microM. The most potent product identified is N-p-chlorophenyl-4-nitrobenzohydroxamic acid with IC(50) value 12microM. The RP-HPLC experiment of these molecules was performed with 50:50(V)/(V) % methanol - water mixture as mobile phase. A QSAR is developed for the human adenocarcinoma cells inhibitory activity of a series of hydroxamic acids (n=1-12) that are structurally related to hydroxyurea. Mult... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1567217 Thu, 01 May 2008 04:00:00 +0100 1567217 http://www.medworm.com/index.php?rid=1567216&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18473917%26dopt%3DAbstract Authors: Oda Y, Kobayashi N, Yamanoi T, Katsuraya K, Takahashi K, Hattori K Three kinds of beta-cyclodextrin derivatives conjugated with glucose moieties, which were expected as models for a drug carrier targeting the drug delivery systems, were designed and synthesized from beta-cyclodextrin and the natural product, 4-hydroxyphenyl-beta-D-glucopyranoside called arbutin. Arbutin was used because it had a phenyl group with a hydroxyl function which could be used to link the glucose moiety to beta-cyclodextrin. The evaluations of these conjugates as the drug-carrying molecules were done by investigating the molecular interactions with the carbohydrate-binding Concanavalin A (Con A) lectin and the anticancer agent, doxorubicin (DXR), using an SPR optical biosensor. The association constan... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1567216 Thu, 01 May 2008 04:00:00 +0100 1567216 http://www.medworm.com/index.php?rid=1567215&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18473918%26dopt%3DAbstract Authors: Becker A, Grecksch G, Schwegler H, Roskoden T The neurotrophic factors play an important role in the maintenance of neurone viability and neuronal communication which are considered to be altered in schizophrenia. Subchronic application of ketamine (Ket) was found to be a useful model in schizophrenia research. To further validate this model the mRNA levels of neurotrophic factors NGF, NT-3, and BDNF and their receptors TrkA, TrkB, and TrkC, respectively, were measured in different brain areas in Ket-pretreated rats subchronically dosed with the atypical antipsychotic drug risperidone (Ris). With the exception of NGF in the frontal cortex, Ket pretreatment did change NGF, NT-3, and BDNF mRNA levels in the frontal cortex, the hippocampus, the striatum, the thalamus/hypothalamus... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1567215 Thu, 01 May 2008 04:00:00 +0100 1567215 http://www.medworm.com/index.php?rid=1567214&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18473919%26dopt%3DAbstract In this report, we demonstrate that LYCD has effects on the transcriptional profile of the human monocytic cell line THP-1. Thirty minute exposures of THP-1 cells with LYCD induced a 6 to 44-fold, dose-dependent increase in the relative expression of the proto-oncogene c-fos in complete media containing 10% FBS or in low serum media containing 0.1% FBS. Furthermore, protein levels of c-Fos rise at 30 minutes of LYCD exposure and remained detectable for at least 120 minutes of LYCD exposure. However, the relative abundance of the c-fos transcript returned to basal levels by 120 minutes. LYCD also induced expression of c-jun with maximal expression of 3-fold at 60 minutes of exposure. Pretreatments with EGFR kinase inhibitor AG-1478 and the MEK1 inhibitor PD98059 blocked the LYCD-dependent i... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1567214 Thu, 01 May 2008 04:00:00 +0100 1567214 http://www.medworm.com/index.php?rid=1567213&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18473920%26dopt%3DAbstract Authors: Kumar PM, Hemalatha R, Mahajan SC, Karthikeyan C, Moorthy NS, Trivedi P To optimize the physiochemical properties of 2-alkoxydihydrocinnamates as PPARalpha/gamma dual agonist, a quantitative structure activity relationship, Hansch approach was made using combination of various thermodynamic, electronic and spatial descriptors. Several regression expressions are obtained using multiple linear regression analysis. The best QSAR model is further validated by leave-one-out cross validation method. Analyses of results from the present QSAR study suggest that for favorable dual PPARalpha/gamma agonist activity electronic property of the substituents in hydrophobic tail phenyl ring plays a key role. The contribution of Hammett constant and dipole moment in the models deduced the impo... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1567213 Thu, 01 May 2008 04:00:00 +0100 1567213 http://www.medworm.com/index.php?rid=1567212&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18473921%26dopt%3DAbstract Authors: Cifuentes G, Bermúdez A, Rodriguez R, Patarroyo MA, Patarroyo ME As microbes use many mechanisms for avoiding immunological pressure, new strategies must be developed to bypass the immunological code of silence of conserved, functionally-important amino acid sequences, such as those involved in high activity binding peptides' (HABPs) attaching to their host cells. Hundreds of experiments in large numbers of Aotus monkeys revealed that this immunological code of silence could be broken by shifting the polarity of some critical host cell binding residues in these HABPs by substituting F for R and vice versa, Y<-->W, L<-->H, I<-->N, P<-->D, M<-->K or E, C<-->T, V<-->N or S; there are special rules for A, G and S. (1)H-nuclear magneti... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1567212 Thu, 01 May 2008 04:00:00 +0100 1567212 http://www.medworm.com/index.php?rid=1567211&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18473922%26dopt%3DAbstract Conclusions: Our observations suggest that soybean oil treatment may be beneficial in type 2 diabetes. Since soybean oil has very high amounts of coenzyme Q and other antioxidants one possible mechanism of action could be as an antioxidant. PMID: 18473922 [PubMed - in process] (Source: Medicinal Chemistry) Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1567211 Thu, 01 May 2008 04:00:00 +0100 1567211 http://www.medworm.com/index.php?rid=1567235&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18336326%26dopt%3DAbstract Authors: Hogan M, Claffey J, Pampillón C, Tacke M From the carbolithiation of 6-morpholino fulvene (3) and different lithiated nitrogen containing heterocycles (2-N-methylimidazolyl, 2-N-(N,N-dimethylamino)methyl-imidazolyl, and 2-N-methylindolyl), the corresponding lithium cyclopentadienide intermediate (4a-c) was formed. These three lithiated intermediates underwent a transmetallation reaction with TiCl(4) resulting in morpholino-functionalised titanocenes 5a-c. When these titanocenes were tested against LLC-PK cells, the IC(50) values obtained were of 24, 36, and 41 microM respectively. The most cytotoxic titanocene in this paper (5a) with an IC(50) value of 24 microM is found to be almost ten times less cytotoxic than cis-platin, which showed an IC(50) value of 3.3 microM when... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1567235 Sat, 01 Mar 2008 05:00:00 +0100 1567235 http://www.medworm.com/index.php?rid=1567234&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18336327%26dopt%3DAbstract Authors: Allil PA, Visconti MA, Castrucci AM, Isoldi MC In vivo and in vitro assays were performed with S91 murine melanoma cells aiming to investigate the effects of testosterone and photoperiod on tumor growth and melanogenesis (tyrosinase activity). In vivo assays were performed by inducing melanoma tumors in castrated mice receiving increasing concentrations of testosterone and submitted to varying photoperiod regimens. The results demonstrated that the increase of melanin content was higher in animals submitted to the longest days, thus demonstrating the importance of photoperiod length in melanin synthesis. Increase in tumor growth and protein content was observed in testosterone-treated animals submitted to 12L:12D; in testosterone-treated animals submitted to 4L:20D and 20L:4D ... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1567234 Sat, 01 Mar 2008 05:00:00 +0100 1567234 http://www.medworm.com/index.php?rid=1567233&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18336328%26dopt%3DAbstract Authors: Russo GL, Ciarcia G, Presidente E, Siciliano RA, Tosti E Marine invertebrates provide a series of natural products with different biological activities. Several of these compounds and their derivatives showed a potent anticancer effect. Tunicates represent an important source of bioactive agents, leading to the isolation of ecteinascidin-743 (ET-743), a compound isolated from the Caribbean sea squirt Ecteinascidia turbinata with a potent cytotoxic activity against a variety of tumours in vitro and in vivo. Current phase II clinical trials against soft tissue sarcomas in Europe and the United States indicate that ET-743 represents a highly promising anticancer agent. Another example is aplidine from the Mediterranean tunicate Aplidium albicans, with a broad spectrum activity ag... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1567233 Sat, 01 Mar 2008 05:00:00 +0100 1567233 http://www.medworm.com/index.php?rid=1567232&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18336329%26dopt%3DAbstract Authors: Sivakumar PM, Doble M Quantitative structure activity relationship (QSAR) studies of selective COX-2 inhibitors of commercial interest (drugs in market and on clinical trials) were performed. The COX-2 inhibitory activity (pIC(50)=-logIC(50)) of these twelve compounds was correlated with nineteen descriptors including steric, electronic and constitutional parameters. pIC(50) activity showed high positive correlation with both volume and HOMO (Highest occupied molecular orbital). A Biparametric model was developed that included both these descriptors. The predictive capability (q(2)= 0.66) of this equation was satisfactory. So it can be used to design newer templates or modify existing templates. Volume is an important parameter for the selective COX-2 inhibitory activity, beca... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1567232 Sat, 01 Mar 2008 05:00:00 +0100 1567232 http://www.medworm.com/index.php?rid=1567231&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18336330%26dopt%3DAbstract Authors: Bontemps Y, Lapierre M, Siegfried G, Calvo F, Khatib AM The proprotein convertases (PCs) are serine proteases involved in various physiological processes and their overactivity or inactivity has been linked to different disorders. PCs are responsible for the proteolytic processing of various polypeptide precursors. Here, we discuss the effect of their N-terminal prosegments on various PC substrates processing and functions. PMID: 18336330 [PubMed - indexed for MEDLINE] (Source: Medicinal Chemistry) Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1567231 Sat, 01 Mar 2008 05:00:00 +0100 1567231 http://www.medworm.com/index.php?rid=1567230&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18336331%26dopt%3DAbstract In conclusion, the modifications performed in this work on reference compounds led us to obtain surprisingly a M(4) selective antagonist. Considering the therapeutic indications for M(4) selective antagonists, compound 2d may serve as a novel lead compound for further optimization. PMID: 18336331 [PubMed - indexed for MEDLINE] (Source: Medicinal Chemistry) Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1567230 Sat, 01 Mar 2008 05:00:00 +0100 1567230 http://www.medworm.com/index.php?rid=1567229&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18336332%26dopt%3DAbstract Authors: Pittalà V, Modica M, Salerno L, Siracusa MA, Guerrera F, Mereghetti I, Cagnotto A, Mennini T, Romeo G The 21-amino acid peptide endothelin-1 (ET-1) is the predominant isoform of the endothelin peptide family, which includes ET-2, and ET-3. These peptides display a variety of physiological activities including vasoconstriction and the stimulation of cell proliferation in tissues both within and outside of the cardiovascular system. They exert their actions via activation of two distinct receptor subtypes, ET(A) and ET(B), belonging to the G protein-coupled receptor (GPCR) superfamily. Ligands of these receptors have received numerous citations in the recent pharmaceutical literature. In particular receptor antagonists, both ET(A)- and ET(B)-selective, as well as non-select... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1567229 Sat, 01 Mar 2008 05:00:00 +0100 1567229 http://www.medworm.com/index.php?rid=1567228&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18336333%26dopt%3DAbstract Authors: Vargas F, Rivas C, Zoltan T, Padrón L, Izzo C, López V, Gómez L, Pujol F, Rangel H, Garzaro D, Fabbro R We have carried out the study of the photochemical properties of a series of synthetic meso-tetraphenylsulfonated porphyrins (TPPMS4) bonded to several metal ions such as: Cu(II), Zn(II), Pd(II), Mn(II), Fe(III), Ni(II) and Co(II) for the optimization of their clinical applications as antiviral agents against the human immunodeficiency virus (HIV-1) as well as the study of the in vitro antiviral photoinactivation mechanisms with future application in blood sterilization. A selective inhibition has been determined in the viral growth (HIV-1) when this is irradiated in the presence of the complex TPPFeS4 and TPPMnS4 (photosensitizer-mediated Type I reaction) as ... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1567228 Sat, 01 Mar 2008 05:00:00 +0100 1567228 http://www.medworm.com/index.php?rid=1567227&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18336334%26dopt%3DAbstract Authors: Sondhi SM, Jain S, Dinodia M, Kumar A A series of thiophene derivatives 1a-d & 2a-c were synthesized by condensation of 5-nitro-2-thiophene carboxaldehyde with mono and diamines respectively. Various imidazole derivatives 3a-c were obtained by condensing 4-(2-ethylamino)-1H-imidazole with 4-acetylpyridine, 2-acetylpyridine and 4-acetylbenzonitrile respectively. Pyridine derivatives 4a-e were synthesized by condensing 2-hydrazino-pyridine with various carbonyl compounds; 5a-c by condensing 2, 6-pyridine dicarbonyl dichloride with various aryl sulfonylhydrazides; 6, 7 by condensing 2, 6-dialdehyde pyridine with 2-hydrazinopyridine and anthranilonitrile respectively and compound 8 by condensing 2, 5-thiophene dialdehyde with hydrazinopyridine. All the compounds were character... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1567227 Sat, 01 Mar 2008 05:00:00 +0100 1567227 http://www.medworm.com/index.php?rid=1567226&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18336335%26dopt%3DAbstract Authors: Belousova EA, Crespan E, Lebedeva NA, Rechkunova NI, Hübscher U, Magaand G, Lavrik OI Translesion synthesis (TLS) is one of the DNA damage tolerance strategies that has evolved to enable orga-nisms to replicate their genome despite the presence of unrepaired damage. TLS complexes are dynamic systems composed of DNA polymerases and associated protein factors. Therefore, it is hard to study these assembles by X-ray analysis or other instrumental methods. Here, we have suggested applying the photoaffinity labeling technique for studying the TLS system in nuclear/cellular extracts. As a tool we proposed to use partial DNA duplexes containing base-substituted photoreactive deoxynucleotides at the 3' end of primer opposite to DNA damage at the template strand. We demonstrated t... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1567226 Sat, 01 Mar 2008 05:00:00 +0100 1567226 http://www.medworm.com/index.php?rid=1567225&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18336336%26dopt%3DAbstract Authors: Khan KM, Ahmed S, Khan ZA, Zia-Ullah , Rani M, Choudhary MI, Perveen S Twenty-five 3-substituted isocoumarins were synthesized using cutting edge microwave-assisted technology in high yields. The syntheses of different isocoumarins were carried out in a single step by the direct condensation of homophthalic acid with aryol and acyl chlorides under the solvent-free conditions without any solid support. The structures of all the synthesized compounds were characterized using different spectroscopic techniques including UV, IR, (1)HNMR and EIMS and purity was confirmed by CHN analysis. All the synthesized compounds were tested for in vitro leishmanicidal activity. Compounds 3a, 3b, 3g, 3l, 3m, 3r, 3t, 3w, 3x, and 3y displayed potential in vitro leishmanicidal activity with IC(50)... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1567225 Sat, 01 Mar 2008 05:00:00 +0100 1567225 http://www.medworm.com/index.php?rid=1567224&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18336337%26dopt%3DAbstract Authors: Zhang H, Hu S, Zhang Y The methodology for predicting the distribution of compounds between Blood and Brain, i.e. their brain/blood partition coefficients (logBB values), was studied using a nonlinear regression analysis in this work. The equations were established on the basis of the different states (neutral, cationic and anionic) of the compounds distributing into the three dominating composition (lipid, protein and water) of the brain. The equations bear strong fitting and predictive power for the distribution of compounds (total set: n=160, r=0.906, s=0.326; training set: n=139, r=0.908, s=0.320; testing set: n=21, r=0.903, s=0.297), and can describe the distribution of the different states of the compounds in three compositions of brain. The compounds in the dataset cont... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1567224 Sat, 01 Mar 2008 05:00:00 +0100 1567224 http://www.medworm.com/index.php?rid=1567223&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18336338%26dopt%3DAbstract Authors: Yerigeri MC, Murari SK, Thimmaiah KN, Math SK, Vishwanath BS The title compounds have been synthesized and tested for structure activity relationship for Phospholipase A2 (PLA2) [E.C. 3.1.1.4] enzyme inhibition. The in vitro anti-tubercular, PLA(2) enzyme inhibitory activities of azetidin-2-one derivatives and in vivo anti-inflammatory studies using mice are highlighted. The analogues of azetidin-2-one were prepared based on the initial activity against Mycobacterium tuberculosis (Mtb). Certain azetidin-2-one analogues described herein showed moderate to good anti-tubercular activity. In particular, two compounds (4f) and (4g) exhibited MIC values of 1.56 and 0.78 microg/mL respectively against the Mtb H(37)Rv strain. Chloro substitution on aryloxy acid apparently enhanced the... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1567223 Sat, 01 Mar 2008 05:00:00 +0100 1567223 http://www.medworm.com/index.php?rid=1567243&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18220966%26dopt%3DAbstract Authors: Giorgioni G, Ruggieri S, Claudi F, Di Stefano A, Ljung E, Carlsson T The novel 4-phenoxy-1,2,3,4-tetrahydroisoquinolines 6a-c and their rigid congeners 4,5,6,6a-tetrahydro-chromeno[2,3,4-de]isoquinolines 7a,b were synthesized in order to obtain dopamine D2-like receptor ligands. The new compounds were evaluated for their in vitro binding affinities, in vivo behavioral activities on rats, and for their effects on rat brain neurochemistry. Compounds 6b (toward both D2 and D3 dopamine receptors) and 7a,b (toward D3 only dopamine receptors) showed the most significant affinities. However none of the new compounds was able to stimulate behavioral activity in non pre-treated rats, nor to influence brain neurochemistry. PMID: 18220966 [PubMed - indexed for MEDLINE] (Source: Medic... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1567243 Tue, 01 Jan 2008 05:00:00 +0100 1567243 http://www.medworm.com/index.php?rid=1567242&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18220967%26dopt%3DAbstract Authors: Otero L, Maya JD, Morello A, Rigol C, Barriga G, Rodríguez J, Folch C, Norambuena E, González M, Azar CO, Cerecetto H, Gambino D In order to get insight into the trypanocidal mechanism of action of a series of 5-nitrofuryl containing thiosemicarbazones some studies related to their bioreduction were performed. Electron spin resonance spectra of radicals generated in T. cruzi by compounds' bioreduction were analyzed. Three different patterns of ESR signals were observed for the different assayed compounds. These results were in agreement with the changes in the T. cruzi-oxygen uptake promoted by these compounds. On the other hand, free-radical scavenger properties, measured as oxygen radical absorbance capacity (ORAC), did not seem to correlate with the trypanocidal a... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1567242 Tue, 01 Jan 2008 05:00:00 +0100 1567242 http://www.medworm.com/index.php?rid=1567241&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18220968%26dopt%3DAbstract Authors: Dixit M, Saeed U, Kumar A, Siddiqi MI, Tamrakar AK, Srivastava AK, Goel A Protein tyrosine phosphatase 1B (PTP1B) is an enzyme that plays a critical role in down-regulating insulin signaling through dephosphorylation of the insulin receptor. Inhibitors of PTP1B showed increased insulin sensitivity and normalize plasma glucose level and thus are useful therapeutic agents for the treatment of diabetes. A series of functionalized 4,5-dihydronaphthofurans and dibenzofurans were synthesized, studied through molecular docking and evaluated for their PTP1B inhibitory activity. PMID: 18220968 [PubMed - indexed for MEDLINE] (Source: Medicinal Chemistry) Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1567241 Tue, 01 Jan 2008 05:00:00 +0100 1567241 http://www.medworm.com/index.php?rid=1567240&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18220969%26dopt%3DAbstract Authors: José CB, Rosales-Hernández MC, Eduardo RS, Abigail B, Carlo ZG, Fabila-Castillo LH, José TF 5-Aminosalicylic acid is one of the drugs most commonly used for inflammatory bowel disease treatment, although its use is limited due to side effects. The aim of this work was to synthesize four 5-ASA derivatives (1-4) and analyze their pharmacological effects. The compound structures were elucidated by spectral (IR and 1H and 13C-NMR) analysis, and their analgesic effects and lethal doses 50 (LD50) were evaluated in the mouse model. In addition, their Log Ps and affinities for both cyclooxygenase enzymes (COX I and COX II) were evaluated through theoretical calculations. All compounds showed analgesic activities from 0.1 mg/Kg to 16 mg/Kg in the mouse model. The imides ... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1567240 Tue, 01 Jan 2008 05:00:00 +0100 1567240 http://www.medworm.com/index.php?rid=1567239&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18220970%26dopt%3DAbstract Authors: Singh J, Singh S, Mishra R, Khadikar PV, Supuran CT, Clare BW, Lakhwani M Mathematical models were developed for the estimation of human carbonic anhydrase (CA) II inhibition. A large set of 95 CA inhibitors incorporating diverse aromatic rings were used for this purpose. The numerical descriptors used were distance- and connectivity- based indices, quantum -theoretical descriptors and Balaban and Balaban type descriptors of molecular structure. After descriptor generation, multiple linear regression analysis was performed to find superior models for estimation. The obtained results indicate that: (i) models based on topological indices are superior to those based on quantum -theoretical descriptors; (ii) combinations of topological and quantum-theoretical descriptors improves... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1567239 Tue, 01 Jan 2008 05:00:00 +0100 1567239 http://www.medworm.com/index.php?rid=1567238&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18220971%26dopt%3DAbstract Authors: Tran JA, Arellano M, Fleck BA, Pontillo J, Marinkovic D, Tucci FC, Wen J, Saunders J, Chen C A series of piperazinephenethylamines were synthesized to study the contribution of a basic amine to binding affinity at the melanocortin-4 receptor. Several potent compounds from this series possessed subnanomolar K(i) values in a competition binding assay. PMID: 18220971 [PubMed - indexed for MEDLINE] (Source: Medicinal Chemistry) Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1567238 Tue, 01 Jan 2008 05:00:00 +0100 1567238 http://www.medworm.com/index.php?rid=1567237&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18220972%26dopt%3DAbstract Authors: Rizza SA, Badley AD HIV protease inhibitors are the backbone of HIV therapy. In addition to blocking intracellular HIV protease and dramatically decreasing viral burden, the protease inhibitors also regulate apoptosis. A growing body of data has confirmed the immunomodulatory effects of HIV protease inhibitors which block CD4+ and CD8+ T cell death in models of HIV infection. The mechanism of this apoptosis inhibition is still under active investigation and supported by several proposed hypothesis for how they alter the fate of the cell. More recently, the anti-apoptotic effects of the HIV protease inhibitors has been extended to the non-HIV, non-immune cell, whereby protease inhibitors prevent apoptosis, and disease, in animal models of sepsis, hepatitis and stroke. Interesti... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1567237 Tue, 01 Jan 2008 05:00:00 +0100 1567237 http://www.medworm.com/index.php?rid=1567236&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18220973%26dopt%3DAbstract Authors: Auer J, Bajorath J A method called "Emerging Chemical Patterns" (ECP) has recently been introduced as a novel approach to binary molecular classification (for example, "active" versus "inactive"). The underlying pattern recognition algorithm was first introduced in computer science and then adopted for applications in medicinal chemistry and compound screening. A special feature is its ability to accurately classify molecules on the basis of very small training sets containing only a few compounds. This feature is highly relevant for virtual compound screening when only very few experimental hits are available as templates. Here we adopt ECP calculations to simulate sequential screening using an experimental high-throughput screening (HTS) data set containing inhibitors of dih... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1567236 Tue, 01 Jan 2008 05:00:00 +0100 1567236 http://www.medworm.com/index.php?rid=1567256&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18045199%26dopt%3DAbstract Authors: Romagnoli R, Baraldi PG, Remusat V, Carrion MD, Cara CL, Cruz-Lopez O, Preti D, Fruttarolo F, Tabrizi MA, Balzarini J, Hamel E Bioisosterism represents one approach used by the medicinal chemist for the rational modification of lead compounds into safer and more clinically effective agents. Bioisosteres are substituents or groups that have chemical or physical similarities and that produce broadly similar biological effects. The sulfone moiety is recognized as a nonclassical bioisostere for replacement of the carbonyl group. When sulfonyl derivatives 5a-e were compared with carbonyl compounds 4a-e, the sulfone substitution dramatically decreased the antiproliferative activity of the series. PMID: 18045199 [PubMed - indexed for MEDLINE] (Source: Medicinal Chemistry) Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1567256 Thu, 01 Nov 2007 04:00:00 +0100 1567256 http://www.medworm.com/index.php?rid=1567255&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18045200%26dopt%3DAbstract Authors: Mehanna AS, Belani JD, Kelley CJ, Pallansc LA A series of thioamides were designed as bio-isosteres to the non-nucleoside reverse transcriptase inhibitor trovirdine by replacement of the thiourea NH groups with methylene groups. Eight thioamides were synthesized and in vitro tested for inhibitory effects on the activity of HIV-1 reverse transcriptase wild and mutant types. Three of the 8-thioamides exhibited enzyme inhibitory activities with IC(50) values below 100 microM. While compound (2) exhibited activity against the mutant strain L100I with IC(50) of 70.1 microM, compound (4) showed activity against the mutant strain K103N with IC(50) of 92.7 microM, and compound (8) with activity against the wild type enzyme with IC(50) of 8.9 microM. Each of the three thioamides could ... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1567255 Thu, 01 Nov 2007 04:00:00 +0100 1567255 http://www.medworm.com/index.php?rid=1567254&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18045201%26dopt%3DAbstract Authors: Carta A, Loriga M, Piras S, Paglietti G, Ferrone M, Fermeglia M, Pricl S, La Colla P, Collu G, Sanna T, Loddo R A series N,N'-bis[4-(1H(2H)-benzotriazol-1(2)-yl)phenyl]alkyldicarboxamides (3a-f and 5a-j) were prepared starting from their already known (1a-d) and (4a-c) or new (4d) amine parents. Because of the antiviral activity of several N-[4-(1H(2H)-benzotriazol-1(2)-yl)phenyl]alkylcarboxamides previously reported, title compounds were evaluated in vitro for cytotoxicity and antiviral activity against viruses representative of Picornaviridae, [i.e. Enterovirus Coxsackie B2 (CVB-2) and Polio (Sb-1)] and of two of the three genera of the Flaviviridae [Bovine Viral Diarrhea Virus (BVDV) and Yellow Fever Virus (YFV)]. Furthermore, because of the in silico activity against the R... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1567254 Thu, 01 Nov 2007 04:00:00 +0100 1567254 http://www.medworm.com/index.php?rid=1567253&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18045202%26dopt%3DAbstract Authors: Boechat N, Kover WB, Bongertz V, Bastos MM, Romeiro NC, Azevedo ML, Wollinger W The design, synthesis and anti HIV-1 replication inhibition of 3-(cyclopropylethynyl)-3-hydroxy-indolin-2-ones, analogues of efavirenz (Sustivatrade mark), are described. Different substituted isatins were used to generate final products that contain pharmacophoric features for RT inhibition, such as the oxoindole and cyclopropylethynyl groups. The suitability of the indolin-2-one ring in the planned compounds in replacement to the benzoxazinone ring of efavirenz was proven, since compound 15 presented a greater activity than efavirenz against HIV-1 replication and was not significantly cytotoxic. PMID: 18045202 [PubMed - indexed for MEDLINE] (Source: Medicinal Chemistry) Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1567253 Thu, 01 Nov 2007 04:00:00 +0100 1567253 http://www.medworm.com/index.php?rid=1567252&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18045203%26dopt%3DAbstract Authors: Reitz AB, Gupta SK, Huang Y, Parker MH, Ryan RR Oxybutynin (1) is a non-selective muscarinic receptor antagonist that is used clinically for the treatment of urinary incontinence. The major metabolite of oxybutynin in humans is desethyloxybutynin (2). We have prepared the enantiomers of 1 and 2 and evaluated their ability to displace N-CT(3)-scopolamine chloride ((3)H-NMS) binding on human cloned muscarinic m1-5 receptors. Compounds 1 and 2 potently displaced (3)H-NMS binding at m1, m3 and m4 receptors, but were less potent at the m2 and m5 subtypes. However, metabolite 2 was more potent than the parent compound 1 in the binding assay. In general the R enantiomers were more potent than their respective S enantiomers. Therefore, we suggest that the cholinergic side effects asso... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1567252 Thu, 01 Nov 2007 04:00:00 +0100 1567252 http://www.medworm.com/index.php?rid=1567251&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18045204%26dopt%3DAbstract Authors: Dhagat U, Carbone V, Chung RP, Matsunaga T, Endo S, Hara A, El-Kabbani O 20alpha-hydroxysteroid dehydrogenase (AKR1C1) plays a key role in the metabolism of progesterone and other steroid hormones, thereby regulating their action at the pre-receptor level. AKR1C1 is implicated in neurological and psychiatric conditions such as catamenial epilepsy and depressive disorders. Increased activity of AKR1C1 is associated with termination of pregnancy and the development of breast cancer, endometriosis and endometrial cancer. Inhibition of the undesired activity of AKR1C1 will help reduce risks of premature birth, neurological disorders and the development of cancer. In order to identify potential leads for new inhibitors of AKR1C1 we adopted a virtual screening-based approach using t... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1567251 Thu, 01 Nov 2007 04:00:00 +0100 1567251 http://www.medworm.com/index.php?rid=1567250&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18045205%26dopt%3DAbstract Authors: Salerno L, Guerrera F, Modica M, Romeo G, Pittalà V, Siracusa MA, Mereghetti I, Cagnotto A, Mennini T In the present study we describe the synthesis of a new series of 1,2,4-triazoles: [3-(arylmethyl)thio-5-aryl-4H-[1,2,4]triazol-4-yl]acetic acids 5a-g, [5-(arylmethyl)thio-3-aryl-1H-[1,2,4]triazol-1-yl]acetic acids 8a-d, and [3-(aryl-methyl)thio-5-aryl-1H-[1,2,4]triazol-1-yl] acetic acids 9a-d. These compounds were tested in binding assays to evaluate their ability as ligands for human ET(A) and ET(B) receptors stably expressed in CHO cells; some of the tested compounds showed affinity in the micromolar range. PMID: 18045205 [PubMed - indexed for MEDLINE] (Source: Medicinal Chemistry) Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1567250 Thu, 01 Nov 2007 04:00:00 +0100 1567250 http://www.medworm.com/index.php?rid=1567249&cid=s_37263_59_f&fid=37263&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18045206%26dopt%3DAbstract Authors: Tsotinis A, Gourgourinis J, Eleutheriades A, Davidson K, Sugden D The synthesis of a series of new N-OMe fluoro-indoles with melatoninergic activity in the Xenopus melanophore assay is described. All of the 4-F substituted compounds, 22a-e and 25a,b, were antagonists on the clonal Xenopus melanophore line. Conversely, the 5-F substituted analogs (15a-e) did not share the same pharmacological profile, as two of them, compounds 15d (R=c-C(3)H(5)) and 15e (R=c-C(4)H(7)), exhibited a weak agonistic and partial agonistic activity, respectively, whilst the other three (15a-c) were all agonists. It seems that in this case the nature of the response (agonist or antagonist activity) is solely dependent on the shape of the R group. PMID: 18045206 [PubMed - indexed for MEDLINE] (Sour... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=1567249 Thu, 01 Nov 2007 04:00:00 +0100 1567249