Medicinal ChemistryThis is an RSS file. You can use it to subscribe to this data in your favourite RSS reader, such as GoogleReader, or to display this data on your own website or blog. Subscribe to this data using MyMedWorm.Subscribe to this data using GoogleReader.Subscribe to this data using Bloglines.Subscribe to this data using MyYahoo.

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Synthesis of Anthraquinone-Ibuprofen Prodrugs with Hydroxyapatite Affinity and Anti-inflammatory Activity Characteristics.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 bi...
Source: Medicinal Chemistry - August 16, 2009 Category: Chemistry Authors: Duan Y, Yu J, Liu S, Ji M Tags: Med Chem Source Type: journals

2-Substituted-5-nitroheterocycles: In vitro Anti-Helicobacter pylori Activity and Structure-activity Relationship Study.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Medicinal Chemistry - August 16, 2009 Category: Chemistry Authors: Foroumadi A, Sorkhi M, Moshafi MH, Safavi M, Rineh A, Siavoshi F, Shafiee A, Emami S Tags: Med Chem Source Type: journals

QSAR Study on Hetaryl Imidazoles: A Novel Dual Inhibitor of VEGF Receptors I and II.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 num...
Source: Medicinal Chemistry - August 16, 2009 Category: Chemistry Authors: Patel A, Karthikeyan C, Moorthy NS, Trivedi P Tags: Med Chem Source Type: journals

A QSAR Study on Some Series of Sodium and Potassium Channel Blockers.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 co...
Source: Medicinal Chemistry - August 16, 2009 Category: Chemistry Authors: Saini L, Gupta SP, Kumar Satluri VS Tags: Med Chem Source Type: journals

Structure-based Design of Benzimidazole Sugar Conjugates: Synthesis, SAR and in vivo Anti-inflammatory and Analgesic Activities.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 pre...
Source: Medicinal Chemistry - August 16, 2009 Category: Chemistry Authors: El-Nezhawy AO, Gaballah ST, Radwan MA, Baiuomy AR, Abdel-Salam OM Tags: Med Chem Source Type: journals

Synthesis and in vitro Transdermal Penetration of Methoxypoly(ethylene glycol) Carbonate Derivatives of Stavudine.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 st...
Source: Medicinal Chemistry - August 16, 2009 Category: Chemistry Authors: N'da DD, Breytenbach JC, Legoabe LJ, Breytenbach JW Tags: Med Chem Source Type: journals

Inhibition of HIV-1 Ribonuclease H Activity by Novel Frangula-emodine Derivatives.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: Medicinal Chemistry - June 28, 2009 Category: Chemistry Authors: Kharlamova T, Esposito F, Zinzula L, Floris G, Cheng YC, Dutschman GE, Tramontano E Tags: Med Chem Source Type: journals

Total Synthesis and Analgesic Activity of 6-Fluoroindan-1-acetic Acid and its 3-Oxo Derivative.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: Medicinal Chemistry - June 28, 2009 Category: Chemistry 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 Tags: Med Chem Source Type: journals

2-Arylbenzimidazoles as Antiviral and Antiproliferative Agents-Part 2.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: Medicinal Chemistry - June 28, 2009 Category: Chemistry Authors: Vitale G, Corona P, Loriga M, Carta A, Paglietti G, La Colla P, Busonera B, Marongiu E, Collu D, Loddo R Tags: Med Chem Source Type: journals

QSAR Investigations on Benzylideneamino and Phenyliminomethyl Scaffolds for Selective COX-2 Inhibiton: A Hansch Approach.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 cros...
Source: Medicinal Chemistry - June 28, 2009 Category: Chemistry Authors: Manivannan , Chaturvedi SC Tags: Med Chem Source Type: journals

Novel Pthalazinyl Derivatives: Synthesis, Antimycobacterial Activities, and Inhibition of Mycobacterium tuberculosis Isocitrate Lyase Enzyme.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 r...
Source: Medicinal Chemistry - June 28, 2009 Category: Chemistry Authors: Sriram D, Yogeeswari P, Senthilkumar P, Dewakar S, Rohit N, Debjani B, Bhat P, Veugopal B, Pavan VV, Thimmappa HM Tags: Med Chem Source Type: journals

Antibacterial Activity of Lipophilic Fluoroquinolone Derivatives.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: Medicinal Chemistry - June 28, 2009 Category: Chemistry Authors: de Almeida CG, Diniz CG, Silva VL, Saraiva MF, Le Hyaric M, de Almeida MV Tags: Med Chem Source Type: journals

Effects of Fluoxetine and Venlafaxine) and Pilocarpine on Rat Parotid Glands.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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,...
Source: Medicinal Chemistry - June 28, 2009 Category: Chemistry Authors: da Silva S, de Azevedo LR, de Lima AA, Ignácio SA, Machado MA, Zaclikevis MV, Grégio AM Tags: Med Chem Source Type: journals

Efficacy of Curcuminoids in Alleviation of Iron overload and Lipid Peroxidation in Thalassemic Mice.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ferrocen...
Source: Medicinal Chemistry - June 28, 2009 Category: Chemistry Authors: Thephinlap C, Phisalaphong C, Fucharoen S, Porter JB, Srichairatanakool S Tags: Med Chem Source Type: journals

Quantitative Structure Activity Relationship Studies of Piperazinyl Phenylalanine Derivatives as VLA-4/VCAM-1 Inhibitors.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 pr...
Source: Medicinal Chemistry - June 28, 2009 Category: Chemistry Authors: Bhargava D, Karthikeyan C, Moorthy NS, Trivedi P Tags: Med Chem Source Type: journals

Synthesis, DNA Binding, Docking and Photoclevage studies of Novel Benzo[b][1,8]naphthyridines.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 publis...
Source: Medicinal Chemistry - June 28, 2009 Category: Chemistry Authors: Naik TR, Naik HS, Naik HR, Bindu PJ, Harish BG, Krishna V Tags: Med Chem Source Type: journals

Increased Serum Endotoxin and Elevated CD14 and IL-1beta Expression in a Rat Model of Cerebrogenic Multiple Organ Dysfunction Syndrome.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 af...
Source: Medicinal Chemistry - June 28, 2009 Category: Chemistry Authors: Chuanqiang Q, Shougang G, Hongzhi G, Chunjuan W, Lin M, Yan H, Lei W, Jianwei L, Xingbang W Tags: Med Chem Source Type: journals

Targets of 3-Bromopyruvate, a New, Energy Depleting, Anticancer Agent.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: Medicinal Chemistry - June 28, 2009 Category: Chemistry Authors: Dell'antone P Tags: Med Chem Source Type: journals

Can Infectious Biofilm be Controlled by Blocking Bacterial Communication?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 lifest...
Source: Medicinal Chemistry - June 28, 2009 Category: Chemistry Authors: José A, Wolf-Rainer Abraham M Tags: Med Chem Source Type: journals

Controlled exploration of structural databases: the case of Farnesyl transferase inhibitors.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Medicinal Chemistry - April 30, 2009 Category: Chemistry Authors: Tizot A, Tucker GC, Pierré A, Hickman J, Goldstein S Tags: Med Chem Source Type: journals

Polyamide curvature and DNA sequence selective recognition: use of 4-aminobenzamide to adjust curvature.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ea...
Source: Medicinal Chemistry - April 30, 2009 Category: Chemistry Authors: Lajiness J, Sielaff A, Mackay H, Brown T, Kluza J, Nguyen B, Wilson WD, Lee M, Hartley JA Tags: Med Chem Source Type: journals

Synthesis and in vitro anti-lung cancer activity of novel 1, 3, 4, 8-Tetrahydropyrrolo [4, 3, 2-de]quinolin-81H-o ne alkaloid analogs.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 mo...
Source: Medicinal Chemistry - April 30, 2009 Category: Chemistry Authors: Nadkarni DH, Wang F, Wang W, Rayburn ER, Ezell SJ, Murugesan S, Velu SE, Zhang R Tags: Med Chem Source Type: journals

Analysis of pralidoxime in serum, brain and CSF of rats.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 antidote...
Source: Medicinal Chemistry - April 30, 2009 Category: Chemistry Authors: Kalász H, Szöko E, Tábi T, Petroianu GA, Lorke DE, Omar A, Alafifi S, Jasem A, Tekes K Tags: Med Chem Source Type: journals

Binding mechanism of H5N1 influenza virus neuraminidase with ligands and its implication for drug design.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: Medicinal Chemistry - April 30, 2009 Category: Chemistry Authors: Gong K, Li L, Wang JF, Cheng F, Wei DQ, Chou KC Tags: Med Chem Source Type: journals

Possible drug candidates for Alzheimer's disease deduced from studying their binding interactions with alpha7 nicotinic acetylcholine receptor.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 mo...
Source: Medicinal Chemistry - April 30, 2009 Category: Chemistry Authors: Gu RX, Gu H, Xie ZY, Wang JF, Arias HR, Wei DQ, Chou KC Tags: Med Chem Source Type: journals

Binding of CYP2C9 with diverse drugs and its implications for metabolic mechanism.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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, Napr...
Source: Medicinal Chemistry - April 30, 2009 Category: Chemistry Authors: Wang JF, Yan JY, Wei DQ, Chou KC Tags: Med Chem Source Type: journals

Structure-activity relationships for serotonin transporter and dopamine receptor selectivity.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 anti...
Source: Medicinal Chemistry - April 30, 2009 Category: Chemistry Authors: Agatonovic-Kustrin S, Davies P, Turner JV Tags: Med Chem Source Type: journals

Olanzapine does not aggrevate ischemic neuronal injury by focal cerebral ischemia: a dose related restriction of the neuroprotective effect?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 eff...
Source: Medicinal Chemistry - April 30, 2009 Category: Chemistry Authors: Yuluğ B, Kilic E Tags: Med Chem Source Type: journals

Synthesis, structural characterization and antibacterial activity of novel 7beta-{[3-(substituted phenyl)-2-propenoyl]amino}-3-[(2,5-dihydro-6-hydroxy-2-methyl)-5-oxo-cis-triazin-3-yl]-thiomethyl-cefalosporins.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ce...
Source: Medicinal Chemistry - April 30, 2009 Category: Chemistry Authors: Rodríguez Z, López MA, González M, Tolón B, Nadal L, González L, Vélez H, Fini A Tags: Med Chem Source Type: journals

Synthesis and comparison of antimalarial activity of febrifugine derivatives including halofuginone.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 resista...
Source: Medicinal Chemistry - April 30, 2009 Category: Chemistry Authors: Samant BS, Sukhthankar MG Tags: Med Chem Source Type: journals

Stepwise regression analysis of the determinants of blood tacrolimus concentrations in chinese patients with liver transplant.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 l...
Source: Medicinal Chemistry - April 30, 2009 Category: Chemistry Authors: Jin Z, Zhang WX, Chen B, Mao AW, Cai WM Tags: Med Chem Source Type: journals

Synthesis and biological evaluation of novel pyrazole derivatives as anti-inflammatory antimicrobial agents.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 6...
Source: Medicinal Chemistry - March 1, 2009 Category: Chemistry Authors: Bekhit AA, Ashour HM, Bekhit Ael-D, Bekhit SA Tags: Med Chem Source Type: journals

Synthesis and Hypoxia Selective Radiosensitization Potential of beta-2-FAZA and beta-3-FAZL: Fluorinated Azomycin beta-Nucleosides.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
(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, ph...
Source: Medicinal Chemistry - March 1, 2009 Category: Chemistry Authors: Kumar P, Emami S, Kresolek Z, Yang J, McEwan AJ, Wiebe LI Tags: Med Chem Source Type: journals

Pharmacokinetics Prediction and Drugability Assessment of Diphenylheptanoids from Turmeric (Curcuma longa L).Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 deriv...
Source: Medicinal Chemistry - March 1, 2009 Category: Chemistry Authors: Balaji S, Chempakam B Tags: Med Chem Source Type: journals

Antioxidative activity, polyphenolic content and anti-glycation effect of some thai medicinal plants traditionally used in diabetic patients.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)...
Source: Medicinal Chemistry - March 1, 2009 Category: Chemistry Authors: Kusirisin W, Srichairatanakool S, Lerttrakarnnon P, Lailerd N, Suttajit M, Jaikang C, Chaiyasut C Tags: Med Chem Source Type: journals

Nanostructured TiO(2) Catalyzed Microwave Assisted Synthesis of Fused Quinolines-DNA Binding, Molecular Docking and Antioxidant Activity.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Medicinal Chemistry - March 1, 2009 Category: Chemistry Authors: Naik HR, Naik HS, Naik TR, Bindu PJ, Naika HR, Aravinda T, Lamani DS Tags: Med Chem Source Type: journals

Derivatives of 1,2,3,4-tetrahydroisoquinoline-7-carboxylic Acid as Novel Fibrinogen Receptor Antagonists.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: Medicinal Chemistry - March 1, 2009 Category: Chemistry Authors: Malovichko OL, Krysko AA, Kabanova TA, Andronati SA, Grishkovets VI, Kachala VV, Panov DA Tags: Med Chem Source Type: journals

beta-Endorphin Fragments DTgammaE and DEgammaE Reduced Morphine Inhibition of Electrically-Induced Contractions and Opiate Withdrawal.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 th...
Source: Medicinal Chemistry - March 1, 2009 Category: Chemistry Authors: Capasso A Tags: Med Chem Source Type: journals

Radioiodinated agents for imaging multidrug resistant tumors.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Medicinal Chemistry - March 1, 2009 Category: Chemistry Authors: Kortylewicz ZP, Augustine AM, Nearman J, McGarry J, Baranowska-Kortylewicz J Tags: Med Chem Source Type: journals

Caulerpenyne binding to tubulin: structural modifications by a non conventional pharmacological agent.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 c...
Source: Medicinal Chemistry - March 1, 2009 Category: Chemistry Authors: Bourdron J, Barbier P, Allegro D, Villard C, Lafitte D, Commeiras L, Parrain JL, Peyrot V Tags: Med Chem Source Type: journals

Preparation and characterisation of alendronate-loaded chitosan microparticles obtained through the spray drying technique.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 propo...
Source: Medicinal Chemistry - March 1, 2009 Category: Chemistry Authors: Ochiuz L, Peris JE Tags: Med Chem Source Type: journals

MenA Is a Promising Drug Target for Developing Novel Lead Molecules to Combat Mycobacterium tuberculosis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: Medicinal Chemistry - March 1, 2009 Category: Chemistry Authors: Kurosu M, Crick DC Tags: Med Chem Source Type: journals

Synthesis, in vitro activities of (2-Cyclopropoxyphenyl)piperidine derivatives for alpha 1a and alpha 1d adrenergic receptor inhibitors.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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, ...
Source: Medicinal Chemistry - January 1, 2009 Category: Chemistry Authors: Li S, Chiu G, Pulito VL, Liu J, Connolly PJ, Middleton SA Tags: Med Chem Source Type: journals

Comparison with Naloxone of Two Dynorphin a Analogues with K- and delta-Opioid Antagonist Activity.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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-a...
Source: Medicinal Chemistry - January 1, 2009 Category: Chemistry Authors: Capasso A Tags: Med Chem Source Type: journals

Exploring the Relationship of Drug-Induced Neutrophil Immaturity & Haematological Toxicity to Drug Chemistry Using Quantitative Structure-Activity Models.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 connect...
Source: Medicinal Chemistry - January 1, 2009 Category: Chemistry Authors: Delieu JM, Horobin RW, Duguid JK Tags: Med Chem Source Type: journals

Synthesis, In Vitro Activities of (2-Cyclopropoxyphenyl)piperidine Derivatives for alpha (1a) and alpha (1d) Adrenergic Receptor Inhibitors.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Medicinal Chemistry - January 1, 2009 Category: Chemistry Authors: Li S, Chiu G, Pulito VL, Liu J, Connolly PJ, Middleton SA Tags: Med Chem Source Type: journals

A Model on the Induction of Adverse Vascular Long-Term Effects of NSAIDs.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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. Th...
Source: Medicinal Chemistry - January 1, 2009 Category: Chemistry Authors: Liedtke RK Tags: Med Chem Source Type: journals

Bicyclol: A Novel Drug for Treating Chronic Viral Hepatitis B and C.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 fib...
Source: Medicinal Chemistry - January 1, 2009 Category: Chemistry Authors: Liu GT Tags: Med Chem Source Type: journals

Effects of Magnetic Stimulation on Oxidative Stress and Skeletal Muscle Regeneration Induced by Mepivacaine in Rat.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: Medicinal Chemistry - January 1, 2009 Category: Chemistry Authors: Jimena I, Tasset I, López-Martos R, Rubio AJ, Luque E, Montilla P, Peña J, Túnez I Tags: Med Chem Source Type: journals

Receptor-Based 3D-QSAR Study for Recognizing True Binding Mode of Mercaptoacyldipeptides at the Active Site of Neutral Endopeptidase.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 o...
Source: Medicinal Chemistry - January 1, 2009 Category: Chemistry Authors: Zaheer-Ul-Haq , Iqbal S Tags: Med Chem Source Type: journals