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. Thu, 25 Aug 2011 04:38:04 +0100 http://www.medworm.com/index.php?rid=4994282&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%3D21711219%26dopt%3DAbstract Authors: Shokeen M, Wadas TJ The increasing use of positron emission tomography in preclinical and clinical settings has widened the demand for radiopharmaceuticals with high specificity that can image biological phenomena in vivo. While many PET tracers have been developed from small organic molecules labeled with carbon-11 or fluorine-18, the short half-lives of these radionuclides preclude their incorporation into radiotracers, which can be used to image biological processes that are not induced immediately after system perturbation. Additionally, the continuing development of targeted agents, such as antibodies and nanoparticles, which undergo extended circulation, require that radionuclides with half-lives that are complimentary to the biological half-lives of these molecules be d... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4994282 Mon, 27 Jun 2011 23:00:00 +0100 4994282 http://www.medworm.com/index.php?rid=4994281&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%3D21711220%26dopt%3DAbstract Authors: Chacko AM, Divgi CR Positron emission tomography (PET) is a powerful molecular imaging technology with the ability to image and monitor molecular events in vivo and in real time. With the increased application of PET radiopharmaceuticals for imaging physiological and pathological processes in vivo, there is a demand for versatile positron emitters with longer physical and biological half-lives. Traditional PET radionuclides, such as carbon-11 ((11)C) and fluorine-18 ((18)F), have relatively short half-lives (20 min and 110 min, respectively). Among the currently available positron emitters, the non-standard radiohalogen iodine-124 ((124)I) has the longest physical half-life at 4.2 d. This, combined with the well characterized radiochemistry of radioiodine, is contributing to t... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4994281 Mon, 27 Jun 2011 23:00:00 +0100 4994281 http://www.medworm.com/index.php?rid=4994280&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%3D21711221%26dopt%3DAbstract This article reviews the cyclotron physics of (89)Zr production, and the chemical separation methods for isolating it from yttrium target material. (89)Zr coordination with the bifunctional chelate desferrioxamine B is discussed, along with the common procedures for attaching the chelate to mAbs. The review is intended to detail the procedure for creating (89)Zr labeled mAbs, going from cyclotron to PET. PMID: 21711221 [PubMed - as supplied by publisher] (Source: Medicinal Chemistry) Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4994280 Mon, 27 Jun 2011 23:00:00 +0100 4994280 http://www.medworm.com/index.php?rid=4994279&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%3D21711222%26dopt%3DAbstract Authors: Nayak TK, Brechbiel MW Development of targeted radionuclide therapy with (90)Y labeled antibodies and peptides has gained momentum in the past decade due to the successes of (90)Y-ibritumomab tiuxetan and (90)Y-DOTA-Phe(1)-Tyr(3)-octreotide in treatment of cancer. (90)Y is a pure β(-)-emitter and cannot be imaged for patient-specific dosimetry which is essential for pre-therapeutic treatment planning and accurate absorbed dose estimation in individual patients to mitigate radiation related risks. This review article describes the utility of (86)Y, a positron emitter (33%) with a 14.7-h half-life that can be imaged by positron emission tomography and used as an isotopically matched surrogate radionuclide for (90)Y radiation doses estimations. This review discusses various aspe... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4994279 Mon, 27 Jun 2011 23:00:00 +0100 4994279 http://www.medworm.com/index.php?rid=4994278&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%3D21711223%26dopt%3DAbstract Authors: Velikyan I Positron Emission Tomography (PET) field and, in particular utilization of (68)Ga radiometal is getting momentum. The development of new imaging agents for targeted, pre-targeted, non-targeted imaging and their clinical applications is accelerating worldwide. The pharmacopoeia monographs regarding generator produced (68)Ga radionuclide and (68)Ga-labeled somatostatin (SST) analogues are in progress. The number of commercial generators and automated synthesizers for (68)Ga-labeling chemistry is increasing constantly. Development of a molecular imaging agent is a complex process including identification of the biological target, respective lead compound, synthesis of the imaging agent, its chemical characterization, pre-clinical, and clinical evaluation. The introduct... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4994278 Mon, 27 Jun 2011 23:00:00 +0100 4994278 http://www.medworm.com/index.php?rid=4994277&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%3D21711224%26dopt%3DAbstract Authors: Gu Y, Huang D, Liu Z, Huang J, Zeng W The labeling of probes with fluorine-18 [(18)F, b(+); 96.7%] continues to play a considerably important role in the development of positron emission tomography (PET) as a modality for both clinical research and clinical diagnoses. This review summarizes the strategies and recent developments in the fluorine-18 labeling of probes for PET imaging. Problems and issues relating to the practical production of fluorine-18 currently in widespread use are also discussed. PMID: 21711224 [PubMed - as supplied by publisher] (Source: Medicinal Chemistry) Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4994277 Mon, 27 Jun 2011 23:00:00 +0100 4994277 http://www.medworm.com/index.php?rid=4994276&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%3D21711225%26dopt%3DAbstract Authors: Cai W PMID: 21711225 [PubMed - as supplied by publisher] (Source: Medicinal Chemistry) Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4994276 Mon, 27 Jun 2011 23:00:00 +0100 4994276 http://www.medworm.com/index.php?rid=4850671&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%3D21568875%26dopt%3DAbstract Authors: Ikeda M, Kurotobi Y, Namikawa A, Kuranuki S, Matsuura N, Sato M, Igarashi Y, Nakamura T, Oikawa T Adiponectin, an adipose-derived protein, shows insulin-sensitizing, anti-diabetic and anti-atherogenic activities, which implies that the protein represents a potential target to improve lifestyle-related diseases like type 2 diabetes. Based on our hypothesis that agents that cause adipocyte differentiation could also act as adiponectin secretion enhancers, we screened butanol extracts of 96 fungus culture extracts for their differentiation-inducing activity in ST-13 preadipocytes. We found that the butanol extract of a fungus P16 culture extract possessed such an activity, and isolated norlichexanthone as an active compound through activity-guided fractionation. Oil red O stainin... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4850671 Sun, 15 May 2011 23:00:00 +0100 4850671 http://www.medworm.com/index.php?rid=4850670&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%3D21568876%26dopt%3DAbstract Authors: Zheng Y, Sun M, Liu Y, Li M, Ji M Several novel quinazolone alkaloids derivatives were synthesized. Some of the target compounds were determined against human prostate cancer DU145 and pancreatic cancer Miacapa2 cells in vitro. The entire compounds had been identified by 1HNMR, 13CNMR, IR, MS and EA. PMID: 21568876 [PubMed - as supplied by publisher] (Source: Medicinal Chemistry) Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4850670 Sun, 15 May 2011 23:00:00 +0100 4850670 http://www.medworm.com/index.php?rid=4850669&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%3D21568877%26dopt%3DAbstract Authors: Tan JJ, Zhang B, Cong XJ, Yang LF, Liu B, Kong R, Kui ZY, Wang CX, Hu LM This discovered and optimized several novel HIV-1 fusion inhibitors and further evaluated the inhibitory activities of these compounds in vitro. Here, we have reported the computer-aided design, synthesis, and biological evaluation of a series of small molecule fusion inhibitors targeting HIV-1 gp41. Based on the structure of inhibitor (NB2), we carried out de novo design and screened out a series of novel structure molecules by using Leapfrog and Autodock programs. Our structure-based modification obtained a potent fusion inhibitor (IC50 = 41.1 µg/mL). Several novel compounds were discovered as fusion inhibitors, which suggested that our design methodology is reliable, paving the way for de novo design ... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4850669 Sun, 15 May 2011 23:00:00 +0100 4850669 http://www.medworm.com/index.php?rid=4850668&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%3D21568878%26dopt%3DAbstract Authors: Carrasco MP, Enyedy EA, Krupenko NI, Krupenko SA, Nuti E, Tuccinardi T, Santamaria S, Rossello A, Martinelli A, Santos MA A set of hydroxamate derivatives of folic acid and methotrexate (MTX) was synthesized and evaluated for the inhibitory activity against histone deacetylase (HDAC) and dihydrofolate reductase (DHFR), two enzymes overexpressed in metastasizing tumors. The synthesized compounds were further screened for their antiproliferative activity in two human cancer cell lines, A549 (non-small cell lung carcinoma) and PC-3 (prostate adenocarcinoma). All derivatives showed significant inhibitory activity against HDACs (micromolar range) while only the MTX derivative was reasonably effective in DHFR inhibition. A docking study provided insight into the binding mode of the ... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4850668 Sun, 15 May 2011 23:00:00 +0100 4850668 http://www.medworm.com/index.php?rid=4850667&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%3D21568879%26dopt%3DAbstract Authors: Montagnani M, Tsivian M, Neri F, Zvi IB, Mantovani I, Nanni P, Benevento M, Simoni P, Marangoni A, Pariali M, Fato R, Bergamini C, Leoni S, Azzaroli F, Mazzella G, Nardo B, Roda E, Aldini R Due to the importance of intestinal transport in pharmacological studies and the emerging role of intestinal signaling activity in the gut-liver axis, we have developed a new method to investigate intestinal transport and liver signaling using cell and serum free mesenteric perfusion system in the rat. The method regarding bile acid active absorption was validated, then, the portal venous content was examined for fibroblast growth factor 15(FGF15), a putative signaling protein produced by the ileal enterocytes following bile acid absorption. After isolation and cannulation of the relevant v... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4850667 Sun, 15 May 2011 23:00:00 +0100 4850667 http://www.medworm.com/index.php?rid=4850666&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%3D21568880%26dopt%3DAbstract Authors: Orenes-Piñero E, Hernández-Romero D, Jover E, de la Morena G, Valdés M, Marín F Hypertrophic cardiomyopathy (HCM) is microscopically characterized by cardiomyocyte hypertrophy, myofibrillar disarray, and fibrosis. During the evolvement of the hypertrophic disease, myocardium suffers a heterogeneous remodeling which includes enhancement of extracellular matrix. The most commonly used pharmacological agents are β- blockers and verapamil, a calcium antagonist, which are the mainstay of therapy. Their proposed mechanisms of effect include improved ventricular relaxation, and increased diastolic filling time but its impact on HCM pathophysiology remains unclear. The results of genetic and pharmacological studies in animal models suggest that cardiac hypertrophy and fibrosis in... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4850666 Sun, 15 May 2011 23:00:00 +0100 4850666 http://www.medworm.com/index.php?rid=4850665&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%3D21568881%26dopt%3DAbstract Authors: Pagadala R, Meshram JS, Chopdea HN, Jettia V, Kusampally U, Udayinic V A simple, highly efficient and environmentally friendly microwave accelerated one-pot synthesis of a series of differently substituted bis-azetidinones have been synthesized expeditiously in good yields from 1,2-diaminoethane and aromatic aldehydes in the presence of zeolite. The structures of the newly synthesized compounds were confirmed by IR, NMR, and mass spectra. The design and calculated molecular properties of all the reported compounds are on the basis of hypothetical antibacterial pharmacophores, which were formulated to interact with microorganisms. A correlation of structure and activity relationship of these compounds with respect to Lipinski rules and drug likeness properties of drugs are desc... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4850665 Sun, 15 May 2011 23:00:00 +0100 4850665 http://www.medworm.com/index.php?rid=4850664&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%3D21568882%26dopt%3DAbstract Authors: Zhang J, Zhang Y, Pan X, Wang S, He L It has been demonstrated that taspine derivatives act as anticancer agents, thus we designed and synthesized a novel class of symmetrical biphenyl derivatives. We evaluated the cytotoxicity and antitumor activity of biphenyls against five human tumor and normal cell lines. The results indicated that the majority of the compounds exhibited anticancer activity equivalent to or greater than the positive control. Compounds (11) and (12) demonstrated the most potent cytotoxic activity with IC50 values between 19.41 µM and 29.27 µM. The potent antiproliferative capabilities of these compounds against ECV304 human transformed endothelial cells indicated that these biphenyls could potentially serve as antiangiogenic agents. We also reviewed the ... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4850664 Sun, 15 May 2011 23:00:00 +0100 4850664 http://www.medworm.com/index.php?rid=4850663&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%3D21568883%26dopt%3DAbstract Authors: Marín LD, Sánchez-Borzone M, García DA Some phenols, like propofol, thymol and related compounds, have been shown to act on the GABAA receptor. Several compounds with GABAergic activity have displayed neuroprotective effects attributed mainly to the potentiation of GABAA-mediated inhibition of synaptic transmission. It has also been found that compounds containing a phenolic OH group can scavenge reactive oxygen species, as in the case of propofol, among others. Thus, the neuroprotective action mechanism of GABAergic phenols would involve both effects, their pharmacological activity on GABAA and their intrinsic antioxidant ability. In this context, the study of the antioxidant properties of phenolic compounds included in the present work will enable these capacities to be c... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4850663 Sun, 15 May 2011 23:00:00 +0100 4850663 http://www.medworm.com/index.php?rid=4850662&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%3D21574948%26dopt%3DAbstract Authors: Mitrasinovic PM, Tomar JS, Nair MS, Barthwal R Trans activation response (TAR) region is an RNA target of considerable importance in controlling the replication cycle of the human immunodeficiency virus (HIV). At a transcriptional level, HIV-1 is regulated by means of the interaction between Tat protein and TAR RNA. The TAR-Tat complex is an attractive target for developing novel antiviral drugs. Herein, the recognition modes of 8 structurally different ligands, as mimics of Tat protein, in complex with a TAR RNA are investigated using the DOCK 6.4 flexible docking protocol in association with the newly-implemented scoring function AMBER including solvation implicitly through the generalized Born solvent-accessible surface area (GB/SA) continuum model. The TAR RNA-ligand inter... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4850662 Sun, 15 May 2011 23:00:00 +0100 4850662 http://www.medworm.com/index.php?rid=4744569&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%3D21486203%26dopt%3DAbstract Authors: Noolvi MN, Patel HM, Bhardwaj V In this paper, an attempt was made to develop a Quantitative Structure Activity Relationship (QSAR) model on a series of quinazoline derivatives acting as Protein tyrosine kinases (erbB-2) inhibitors using Multiple Linear Regression, Principal Component Regression and Partial Least Squares Regression methods. Among these three methods, Multiple Linear Regression (MLR) method has come out with a very promising result as compared to other two methods. Various 2D descriptors were calculated and used in the present analysis. For model validation, the dataset was divided into training and test sets using spherical exclusion method. The developed MLR- QSAR model was found to be statistically significant with respect to training (r2 =0.956), cross-vali... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4744569 Sun, 10 Apr 2011 23:00:00 +0100 4744569 http://www.medworm.com/index.php?rid=4744568&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%3D21486204%26dopt%3DAbstract Authors: Khan KM, Khan M, Ali M, Taha M, Hameed A, Ali S, Perveen S, Choudhary MI Twenty-four derivatives of N,N-dimethylbarbituric acid 1-24 were screened for their DPPH radical scavenging activity. These compounds showed an excellent antioxidant activity. A structure-activity relationship has been discussed, while all the synthetic compounds were characterized by spectroscopic techniques and elemental analysis. PMID: 21486204 [PubMed - as supplied by publisher] (Source: Medicinal Chemistry) Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4744568 Sun, 10 Apr 2011 23:00:00 +0100 4744568 http://www.medworm.com/index.php?rid=4744567&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%3D21486205%26dopt%3DAbstract In conclusion, the anti-oxidative effects of Apo-bLF and Fe-bLf studied for the first time, show dynamic changes that may allow for necessary protection from imbalanced oxidative conditions, and potential at reducing the ability of cancer cells to protect themselves from oxidative stress states. PMID: 21486205 [PubMed - as supplied by publisher] (Source: Medicinal Chemistry) Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4744567 Sun, 10 Apr 2011 23:00:00 +0100 4744567 http://www.medworm.com/index.php?rid=4744566&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%3D21486206%26dopt%3DAbstract Authors: Lima CH, Henriques MG, Candéa AL, Lourenço MC, Bezerra FA, Ferreira ML, Kaiser CR, de Souza MV A series of nine N'-(E)-heteroaromatic-pyrazine-2-carbohydrazide derivatives (5a-f and 6a-c) have been synthesized and evaluated against M. tuberculosis ATCC 27294 using the micro plate Alamar Blue assay (MABA), being the activities expressed as the minimum inhibitory concentration (MIC) in µg/ml. Compounds 5a and 5f exhibited potent activities (3.12 and 50µg/mL, respectively) when compared to the first line drug pyrazinamide (MIC>100 µg/mL). Afterwards, these compounds were evaluated for their cell viabilities in non-infected and infected macrophages with Mycobaterium bovis Bacillus Calmette-Guerin (BCG) and 5f was not cytotoxic to host cells in the effective concentration t... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4744566 Sun, 10 Apr 2011 23:00:00 +0100 4744566 http://www.medworm.com/index.php?rid=4744565&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%3D21486207%26dopt%3DAbstract In conclusion, we were able to obtain a semi-synthetic biomaterial with tunable physico-chemical properties, which can be used to develop new nanosystems with the ability to associate genetic material. We therefore propose that the gelatin, with its chemical modification, provide a unique biomaterial for the development of new nanomedicines. PMID: 21486207 [PubMed - as supplied by publisher] (Source: Medicinal Chemistry) Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4744565 Sun, 10 Apr 2011 23:00:00 +0100 4744565 http://www.medworm.com/index.php?rid=4744564&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%3D21486208%26dopt%3DAbstract Authors: Seubsasana S, Pientong C, Ekalaksananan T, Thongchai S, Aromdee C Andrographolide (AD), and 14-deoxyandrographolide (DAD) isolated from Andrographis paniculata Nees, Acanthaceae, and 3,19-isopropylideneandrographolide (IPAD), a semi-synthetic compound of AD, were examined for anti-HSV-1 activity in vitro. The inhibitory effects of these compounds on viral entry and replication steps were determined using pre- and post-infection assays, respectively. All the three compounds exhibited less than 50% inhibitory act against viral entry. In the post-infection, IPAD displayed absolute inhibition, whereas AD and DAD gave moderate activity. IPAD was selected to determine for the stage of anti-replication by time-of-addition and time-of-removal assays. From the time of removal assay, IP... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4744564 Sun, 10 Apr 2011 23:00:00 +0100 4744564 http://www.medworm.com/index.php?rid=4744563&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%3D21486209%26dopt%3DAbstract Authors: Santos RN, Guido RV, Oliva G, Dias LC, Andricopulo AD Migrastatin, a macrolide natural product, and its structurally related analogs are potent inhibitors of cancer cell metastasis, invasion and migration. In the present work, a specialized fragment-based method was employed to develop QSAR models for a series of migrastatin and isomigrastatin analogs. Significant correlation coefficients were obtained (best model, q2 = 0.76 and r2 = 0.91) indicating that the QSAR models possess high internal consistency. The best model was then used to predict the potency of an external test set, and the predicted values were in good agreement with the experimental results (R2 pred = 0.85). The final model and the corresponding contribution maps, combined with molecular modeling studies, prov... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4744563 Sun, 10 Apr 2011 23:00:00 +0100 4744563 http://www.medworm.com/index.php?rid=4744562&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%3D21486210%26dopt%3DAbstract Authors: Ojha PK, Roy K Resistance of available antimalarial drugs against Plasmodium species is one of the major problems of malaria control in the developing world. In the present study, we have performed QSAR, pharmacophore mapping and molecular docking studies of cycloguanil derivatives as Plasmodium falciparum dihydrofolate reductase thymidylate synthase (PfDHFR-TS) inhibitors to explore essential features required for the antimalarial activity and important interaction patterns between the enzyme and ligands for the design of new potent PfDHFR-TS inhibitors. The QSAR studies have been carried out using topological parameters along with thermodynamic and structural descriptors. Acceptable values of internal and external validation parameters for the developed QSAR models confirm a... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4744562 Sun, 10 Apr 2011 23:00:00 +0100 4744562 http://www.medworm.com/index.php?rid=4744561&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%3D21486211%26dopt%3DAbstract Authors: Kamal A, Srikanth YV, Ashraf M, Naseer M, Khan A, Shaik TB, Kalivendi SV, Suri N, Saxena AK Two series of compounds (5-14 and 15-23) based on the scaffolds of 2-(1,1-dioxido-4-phenyl-4Hbenzo[e][1,2,4]thiadiazin-3-yl)-N-(4-methoxyphenyl)hydrazinecarboxamide (5) and 2-((4-methoxyphenyl)amino)-10-phenyl-10H-benzo[e][1,2,4]triazolo[1,5-b][1,2,4]thiadiazine 5,5-dioxide (15) respectively, were designed and synthesized. These compounds were tested for anticancer activity against various cancer cell lines including lung, ovary, prostate, breast and colon cancers. They exhibited moderate to good inhibitory activity against the above cell lines and compound 9 was found to be the most active one from these two series. Further studies showed that cancer cell growth inhibition by compounds... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4744561 Sun, 10 Apr 2011 23:00:00 +0100 4744561 http://www.medworm.com/index.php?rid=4744560&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%3D21486212%26dopt%3DAbstract Authors: Barlow JW, Zhang T, Woods O, Byrne AJ, Walsh JJ In an investigation of 4-amino-3,4-dihydronaphthalen-1(2H)-ones as novel modulators of allergic and inflammatory phenomena, we have investigated a series of cyclic analogues. Tertiary amines of structural types 9, 10, 20 and 21 were synthesised and evaluated for mast cell stabilising activity. In vitro and in vivo studies showed that of these compounds, the cyclohexenylamino derivatives of tetralone and benzosuberone of series 20 and 21 exhibited interesting activity both in vitro and in vivo. PMID: 21486212 [PubMed - as supplied by publisher] (Source: Medicinal Chemistry) Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4744560 Sun, 10 Apr 2011 23:00:00 +0100 4744560 http://www.medworm.com/index.php?rid=4456298&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%3D21222608%26dopt%3DAbstract Authors: Jaikang C, Chaiyasut C, Narongchai P, Niwatananun K, Narongchai S, Kusirisin W Ethyl caffeate (EC), octyl caffeate(OC), benzyl caffeate(BC) and phenethyl caffeate(PC) were synthesized and evaluated for scavenging of superoxide anion, nitric oxide radical and 1,1-diphenyl-1-picrylhydrazyl radical(DPPH). Antioxidant activity was investigated with reducing power method. Pooled human liver microsome was used for investigating the effects on cytochrome P450 1A2 (CYP1A2) catalytic activities by using phenacetin as a substrate. Dixon and Cornish-Bowden plots were used for enzyme kinetic analysis. The EC, OC, BC and PC potentially inhibited superoxide anion, nitric oxide and DPPH radicals. IC(50) values of superoxide anion scavenging of EC, OC, BC and PC were 16.42, 79.83, 123.69 and ... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4456298 Tue, 11 Jan 2011 00:00:00 +0100 4456298 http://www.medworm.com/index.php?rid=4456297&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%3D21222609%26dopt%3DAbstract Authors: Nam NH, Dung PT, Thuong PT A series of 2-phenylbenzothiazoles has been synthesized either by i) condensation of different aromatic aldehydes with 2-aminothiophenol or ii) condensation of N-(2-chlorophenyl)benzothioamides in KOH catalyzed by potassium fericyanide. The structures of synthesized compounds were confirmed by IR, MS, and (1)H-NMR. The results of biological activity screening showed that six compounds including 2-phenylbenzothiazol (1a), 2-(2-chlorophenyl)benzothiazole (1b), 2-(3-chlorophenyl)benzothiazole (1c), 2-(4-hydroxyphenyl)benzothiazole (1e), 2-(4-dimethylaminophenyl)benzothiazole (1h) and 2-(2,3,4-trimethoxyphenyl)benzothiazole (1i) exhibited significant antibacterial activities; two compounds (1a, 1e) exhibited antifungal activities. Especially, 1e showed c... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4456297 Tue, 11 Jan 2011 00:00:00 +0100 4456297 http://www.medworm.com/index.php?rid=4456296&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%3D21222610%26dopt%3DAbstract Authors: Ferreira LG, Leitão A, Montanari CA, Andricopulo AD Several protease inhibitors have reached the world market in the last fifteen years, dramatically improving the quality of life and life expectancy of millions of HIV-infected patients. In spite of the tremendous research efforts in this area, resistant HIV-1 variants are constantly decreasing the ability of the drugs to efficiently inhibit the enzyme. As a consequence, inhibitors with novel frameworks are necessary to circumvent resistance to chemotherapy. In the present work, we have created 3D QSAR models for a series of 82 HIV-1 protease inhibitors employing the comparative molecular field analysis (CoMFA) method. Significant correlation coefficients were obtained (q(2) = 0.82 and r(2) = 0.97), indicating the internal co... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4456296 Tue, 11 Jan 2011 00:00:00 +0100 4456296 http://www.medworm.com/index.php?rid=4456295&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%3D21222611%26dopt%3DAbstract Authors: Cai L, Wang Y, Wang JF, Chou KC Human SP110 plays an important role in resisting intracellular pathogens, and hence has become an important drug target for preventing intracellular pathogen diseases, such as tuberculosis, hepatic veno-occlusive disease, and intracellular cancers. Unfortunately, so far little is known about the interactions of SP110 with the other proteins in a cell, which is considered to be the key for revealing its action mechanism and mediated pathway. Using both the genetic and structural analyses as well as the segment-docking approach, we have identified two proteins: the human remodeling and spacing factor 1 (RSF1) and the activating transcription factor 7 interacting protein (ATF7IP). They are very likely interacting with human SP110 during the process... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4456295 Tue, 11 Jan 2011 00:00:00 +0100 4456295 http://www.medworm.com/index.php?rid=4456294&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%3D21222612%26dopt%3DAbstract We report here a strategy to synthesize a series of E2-furanic derivatives from E1. An intermediate epoxide was first obtained and then reduced to give a furanic steroid, which allowed us to introduce a molecular diversity like alcohol, bromide, ester, acid and amide. The inhibition of the transformation of [(14)C]-E1 (100 nM) into [(14)C]-E2 by these compounds was first evaluated with homogenated HEK-293 cells overexpressing 17β-HSD1. The epoxide and butylamide derivatives showed the best inhibitions with 72% and 66%, respectively, at 10 µM. All furanic compounds showed a lower 17β-HSD1 inhibitory potency in intact T47-D breast cancer cells than in homogenated cells, but a great improvement of the inhibitory activity was observed for the epoxide, which gave 62% and 90% of inhibition of... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4456294 Tue, 11 Jan 2011 00:00:00 +0100 4456294 http://www.medworm.com/index.php?rid=4456293&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%3D21222613%26dopt%3DAbstract This article was aimed to give an overview of steroid treatment for protection of the inner ear against various cochlear injuries. Findings obtained from animal studies are focused on. PMID: 21222613 [PubMed - as supplied by publisher] (Source: Medicinal Chemistry) Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4456293 Tue, 11 Jan 2011 00:00:00 +0100 4456293 http://www.medworm.com/index.php?rid=4456292&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%3D21222614%26dopt%3DAbstract Authors: Valverde E, Torres E, Guardiola S, Naesens L, Vázquez S The reaction of a series of 1,2-diols with thionyl chloride led to bisnoradamantane sulfites in very good yields. The reaction has also been applied to related polycyclic scaffolds. The compounds have been tested for antiviral activity but none of them showed to be active. Several attempts to generate and trap SO from these polycyclic sulfites have been unsuccessful. PMID: 21222614 [PubMed - as supplied by publisher] (Source: Medicinal Chemistry) Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4456292 Tue, 11 Jan 2011 00:00:00 +0100 4456292 http://www.medworm.com/index.php?rid=4456291&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%3D21222615%26dopt%3DAbstract Authors: Musa MA, Zhou A, Sadik OA The synthesis and antiproliferative activity of new coumarin-based benzopyranone derivatives containing basic amino side chain are described. The cytotoxicities against A549 and MCF-7 human cancerous cell lines were determined after 24, 48, 72h drug exposure employing MTT assay at concentrations ranging from 0-100 μM. The antiproliferative activities of these compounds were compared to tamoxifen (TAM), 4-hydroxytamoxifen (4-OHT), raloxifene (RAL), 17β-estradiol (E2) and Diethylstilbestrol (DES). In vitro results indicated that compounds 10 and 12 were the most potent showing significant inhibitory activities against these cell lines. Furthermore, their antiproliferative activity against MCF-7 human breast cancer cell line is comparable to that of TA... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4456291 Tue, 11 Jan 2011 00:00:00 +0100 4456291 http://www.medworm.com/index.php?rid=4456290&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%3D21222616%26dopt%3DAbstract Authors: Lyakhovich A, Michlmayr A, Bakulina A, Gerner C, Oehler R, Gasche C 5-aminosalicylic acid (5-ASA or mesalazine) is widely used for treatment of inflammatory bowel disease and considered to be cancer preventive. Still, the molecular mechanisms explaining its properties remain largely unknown, partially due to the lack of instrumentarium needed to identify its array of molecular targets. Modern OMICs-based technologies utilized in this study may serve as a powerful and unbiased tool to search for such targets. Here we demonstrate that 5-ASA alters β-catenin immunocomplex formation by changing complex binding of seven proteins including translation initiation factors eIF4b. OMICs-based cross-testing by reverse in-gel chemogenomics (utilizing 5-ASA's fluorescent properties), in-s... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4456290 Tue, 11 Jan 2011 00:00:00 +0100 4456290 http://www.medworm.com/index.php?rid=4456288&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%3D21222617%26dopt%3DAbstract Authors: Wang Y Lung cancer is a leading cause of death in human. Cancer stem cells have been regarded as basis for failure of current therapeutic options. Salinomycin was shown to kill these cancer stem cells in some types of cancer such as breast cancer and leukemia. The in vitro anticancer activities of salinomycin have been validated against the lung cancer cell line A549 via sulforhodamine B and colony formation assay. Salinomycin has been demonstrated to significantly rupture the in vitro lung cancer tumorospheres from ALDH positive A549 lung cells using flow cytometry. Expression of stem cell markers OCT-4, NANOG and SOX2 in ALDH positive A549 lung cells was decreased significantly by real-time RT-PCR analysis after 24 hour salinomycin treatment. Taken together, salinomycin may ... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4456288 Tue, 11 Jan 2011 00:00:00 +0100 4456288 http://www.medworm.com/index.php?rid=4456287&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%3D21235513%26dopt%3DAbstract Authors: Al-Shuneigat J, Qing Y, Beale P, Fisher K, Huq F A new trinuclear platinum compound [{trans-PtCl(NH(3))(2)}(2)⎨trans-Pt(thiazole) (2)⎬{H(2)N(CH(2))(6)NH(2)}(2)]Cl(3) (NO(3)) has been synthesized and characterized. The activity of the compound against three human ovarian cancer cell lines A2780, A2780(cisR) and A2780(ZD0473R), its cell uptake and level of binding with DNA have been determined. JH5 is found to be less active than cisplatin against parent A2780 cell line but more active than cisplatin against the A2780(cisR) and A2780(ZD0473R) resistant cell lines indicated by the lower resistance factors. The results indicate that at the level of its activity JH5 has been better able to overcome mechanisms of resistance operating in A2780(cisR) and A2780(ZD0473R) cell lines.... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4456287 Sat, 01 Jan 2011 00:00:00 +0100 4456287 http://www.medworm.com/index.php?rid=4456286&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%3D21235514%26dopt%3DAbstract Authors: De Caro V, Giandalia G, Siragusa MG, Lamartina L, Friscia S, Sardo P, Carletti F, Rizzo V, Ferraro G, Giannola LI A new aminoacidic derivative of valproic acid (VPA) has been synthesized and characterized by analytical and spectral data. The rationale for the preparation of such potential antiepileptic agent is based on the observation that chemical combination of the anticonvulsant pharmacophore, VPA with essential aminoacids could afford more effective and less toxic actives. The synthesis, characterization, physico-chemical parameters functional for crossing Blood Brain Barrier of N-valproyl-L-tryptophan (4) are reported. The Log D (pH7.4) (0.3) indicates that (4) is adequate to cross biological membranes. Its chemical and enzymatic stability were assessed. The experiments ... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4456286 Sat, 01 Jan 2011 00:00:00 +0100 4456286 http://www.medworm.com/index.php?rid=4456285&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%3D21235515%26dopt%3DAbstract Authors: Li N, He J, Zhan Y, Zhou N, Zhang J A series of novel imperatorin derivatives were synthesized from commercially available xanthotoxin. The in vitro pharmacological evaluation indicated that all of the compounds possessed potent vasodilatory activity. Among them, compounds (5b), (5d) and (5e) exhibited higher vasdilatory activity (with EC(50) values of 0.68 µM, 0.59 µM and 0.49 µM, respectively) than imperatorin (EC(50) = 1.12 µM). The program Volsurf was used to predict the derivatives' ADME-relevant descriptors. The results suggested that these novel compounds had a potential interest for the development of novel and potent vasorelaxant agents. PMID: 21235515 [PubMed - in process] (Source: Medicinal Chemistry) Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4456285 Sat, 01 Jan 2011 00:00:00 +0100 4456285 http://www.medworm.com/index.php?rid=4456284&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%3D21235516%26dopt%3DAbstract Authors: Liao QH, Gao QZ, Wei J, Chou KC EGFR is the cell-surface receptor. Its overexpression or overactivity has been associated with a number of cancers, including breast, lung, ovarian, and anal cancers. Many therapeutic approaches are aimed at the EGFR. A series of 2, 7-diamino-thiazolo [4,5-d] pyrimidine analogues are among the most highly potent and selective inhibitors of EGFR described to date. For in-depth investigation into the structural and chemical features responsible for the binding recognition mechanism concerned, as well as for exploring the binding pocket of these compounds, we performed a series of automated molecular docking operations. It was revealed that the binding site consisted of three main areas (P1, P2 and P3) composed of most of the hydrophobic amino acid... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4456284 Sat, 01 Jan 2011 00:00:00 +0100 4456284 http://www.medworm.com/index.php?rid=4456280&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%3D21235517%26dopt%3DAbstract Authors: Luan Y, Ma C, Sui Z, Wang X, Feng J, Liu N, Jing F, Wang Y, Li M, Fang H, Xu W Aminopeptidase N (APN) is a ubiquitous enzyme overexpressed on tumor cells and plays an important role in angiogenesis and metastasis of tumor. Bestatin as an effective inhibitor of aminopeptidase N is used for complementary treatment of cancer with other drugs. In this work, we reformed the structure of bestatin to a new derivative LYP3 to improve the water solubility and effectiveness. The inhibitory activity of LYP3 against APN was evaluated in vitro. PMID: 21235517 [PubMed - in process] (Source: Medicinal Chemistry) Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4456280 Sat, 01 Jan 2011 00:00:00 +0100 4456280 http://www.medworm.com/index.php?rid=4456279&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%3D21235518%26dopt%3DAbstract In conclusion, this study has identified several quinone derivatives, such as NQ, that are promising anti-inflammatory candidates. PMID: 21235518 [PubMed - in process] (Source: Medicinal Chemistry) Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4456279 Sat, 01 Jan 2011 00:00:00 +0100 4456279 http://www.medworm.com/index.php?rid=4456278&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%3D21235519%26dopt%3DAbstract Authors: Pintér G, Bereczki I, Rőth E, Sipos A, Varghese R, Udo EE, Ostorházi E, Rozgonyi F, Phillips OA, Herczegh P A novel series of tetraethylene glycol (TEG) triazolyl and squaramide containing oxazolidinones were synthesized and tested for their antibacterial activity against a selected panel of Gram-positive and Gram-negative bacteria. The 4-TEG-triazolyl derivatives were prepared by 'click reaction'. The introduction of the TEG and squaramide groups did not favor antibacterial activity. The three nucleoside-containing oxazolidinones were also prepared by 'click' methodology resulted in weak antibacterial activity. PMID: 21235519 [PubMed - as supplied by publisher] (Source: Medicinal Chemistry) Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4456278 Sat, 01 Jan 2011 00:00:00 +0100 4456278 http://www.medworm.com/index.php?rid=4456277&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%3D21235520%26dopt%3DAbstract Authors: Jain J, Kumar Y, Sinha R, Kumar R, Stables J A series of ten compounds (Compounds J(1)-J(10)) of (±) 3-menthone aryl acid hydrazone was synthesized and characterized by thin layer chromatography and spectral analysis. Synthesized compounds were evaluated for anticonvulsant activity after intraperitoneal (i.p) administration to mice by maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) induced seizure method and minimal clonic seizure test. Minimal motor impairment was also determined for these compounds. Results obtained showed that four compounds out of ten afforded significant protection in the minimal clonic seizure screen at 6 Hz. Compound J(6), 4-Chloro-N-(2-isopropyl-5-methylcyclohexylidene) benzohydrazide was found to be the most active compound wit... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4456277 Sat, 01 Jan 2011 00:00:00 +0100 4456277 http://www.medworm.com/index.php?rid=4456276&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%3D21235521%26dopt%3DAbstract Authors: Thephinlap C, Phisalaphong C, Lailerd N, Chattipakorn N, Winichagoon P, Vadolus J, Fucharoen S, Porter JB, Srichairatanakool S Non-transferrin bound iron (NTBI) is found in plasma of β-thalassemia patients and causes oxidative tissue damage. Cardiac siderosis and complications are the secondary cause of death in β-thalassemia major patients. Desferrioxamine (DFO), deferiprone (DFP) and deferasirox (DFX) are promising chelators used to get negative iron balance and improve life quality. DFP has been shown to remove myocardial iron effectively. Curcuminoids (CUR) can chelate plasma NTBI, inhibit lipid peroxidation and alleviate cardiac autonomic imbalance. Effects of CUR on cardiac iron deposition and function were investigated in iron-loaded mice. Wild type ((mu)β(+/+) WT) a... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4456276 Sat, 01 Jan 2011 00:00:00 +0100 4456276 http://www.medworm.com/index.php?rid=4145424&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%3D21054274%26dopt%3DAbstract Authors: Ahmed NS, Gary BD, Piazza GA, Tinsley HN, Laufer S, Abadi AH Starting from a previously reported lead compound GR30040X (a hydantoin tetrahydro-β-carboline derivative with a 4- pyridinyl ring at C- 5), a series of structurally related tetrahydro-β-carboline derivatives were prepared. The tetrahydro-β-carboline skeleton was fused either to a hydantoin or to a piperazindione ring, the pendant aryl group attached to C-5 or C-6 was changed to a 3, 4-dimethoxyphenyl or a 3-pyridinyl ring; different N-substituents on the terminal ring were introduced, a straight chain ethyl group, a branched tert. butyl and P-chlorophenyl group rather than n-butyl group of the lead compound. All four possible diastereomers of target tetrahydro-β-carboline derivatives were prepared, separated by ... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4145424 Mon, 08 Nov 2010 00:00:00 +0100 4145424 http://www.medworm.com/index.php?rid=4145423&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%3D21054275%26dopt%3DAbstract Authors: Romagnoli R, Baraldi PG, Pavani MG, Cruz-Lopez O, Hamel E, Balzarini J, Brognara E, Zuccato C, Gambari R Microtubules are dynamic structures that play a crucial role in cellular division and are recognized as an important target for cancer therapy. In search of new compounds with strong antiproliferative activity and simple molecular structure, we have synthesized four different series of compounds in which different substituents were linked to the 4- or 5-position of the 2-amino-3-(3',4',5'-trimethoxybenzoyl) thiophene system. When these compounds were analyzed in vitro for their inhibition of cell proliferation, the 4-aryl substituted derivatives had little activity. In contrast, the presence of a methylene, oxymethyl, aminomethyl or methylenepiperazino moiety between the ar... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4145423 Mon, 08 Nov 2010 00:00:00 +0100 4145423 http://www.medworm.com/index.php?rid=4145422&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%3D21054276%26dopt%3DAbstract In this study, a prediction method based on Nearest Neighbor Algorithm and a novel metric, which was obtained by combining compound similarity and functional domain composition, was proposed. The target proteins were divided into the following groups: enzymes, ion channels, G protein-coupled receptors, and nuclear receptors. As a result, four predictors with the optimal parameters were established. The overall prediction accuracies, evaluated by jackknife cross-validation test, for four groups of target proteins are 90.23%, 94.74%, 97.80%, and 97.51%, respectively, indicating that compound similarity and functional domain composition are very effective to predict drug-target interaction networks. PMID: 21054276 [PubMed - as supplied by publisher] (Source: Medicinal Chemistry) Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4145422 Mon, 08 Nov 2010 00:00:00 +0100 4145422 http://www.medworm.com/index.php?rid=4145421&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%3D21054277%26dopt%3DAbstract Authors: Rajesh RP, Ramasamy MS, Murugan A The cytotoxicity-based chemotherapy treatment for cancer has significant side effects. Therefore, anticancer research is concentrated on identifying an effective drug with minimal side effects. The methanol extract of ascidian Polyclinum indicum and its column fraction PI-8 showed cytotoxicity against cervical cancer cells (HeLa) with an IC(50) of 77.5 µg/mL and 1.12 µg/mL. Hoechst staining with PI-8 treated cells portrayed the apoptotic events in drug-induced apoptosis. The PI-8 markedly arrested G(2)/M and S phases in cell cycle. The occurrence of a second population of apoptotic cells in the range of lower Forward Scatter (FSC) and higher Side Scatter (SSC) compared to control cells indicated the characteristic feature of the cells dying ... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4145421 Mon, 08 Nov 2010 00:00:00 +0100 4145421 http://www.medworm.com/index.php?rid=4121340&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%3D20977412%26dopt%3DAbstract Authors: Zeng HH, Wan LH Thioredoxin reductase plays a critical role in the regulation of cancer cell apoptosis, making it an attractive target for the design of new anticancer drugs. Several classes of compounds have been considered as potential antitumor or chemopreventive agents; most of them apparently interact with thioredoxin reductase's C-terminal redox center. PMID: 20977412 [PubMed - as supplied by publisher] (Source: Medicinal Chemistry) Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4121340 Mon, 25 Oct 2010 00:00:00 +0100 4121340 http://www.medworm.com/index.php?rid=4121339&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%3D20977413%26dopt%3DAbstract Authors: Holmes EM, Breytenbach JC, Gerber M, du Plessis J The aim of this study was to investigate the effects of different ester groups in position 5' of stavudine on the transdermal penetration with and without the use of Pheroid™ as the delivery system. Six esters were prepared by reaction of stavudine with six different acid chlorides at room temperature. Female human abdominal skin was used for in vitro penetration in Franz diffusion cells. The experimental aqueous solubility of stavudine (104.75 mg/mL) was much higher than that of the synthesized derivatives (ranging from 0.08 to 5.17 mg/mL), while the log D (octanol-buffer partition coefficient) of stavudine (-0.85) was lower than that of its derivatives (ranging from -0.41 to 3.06). The experimental transdermal flux of stavu... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4121339 Mon, 25 Oct 2010 00:00:00 +0100 4121339 http://www.medworm.com/index.php?rid=4121338&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%3D20977414%26dopt%3DAbstract Authors: Karolidis DA, Agatonovic-Kustrin S, Morton DW Dopamine and its receptors play a critical role in diseases such as Parkinson's disease and schizophrenia. A problem with developing specific drugs for such diseases is that there are five subtypes of dopamine receptors that can be categorized as either D1 like or D2 like. Since the binding sites are quite similar, it is difficult to design the subtype specific agonists and antagonists required for therapy with minimal side effects. Thus, the aim of this study was to identify the molecular characteristics important to the selective binding of dopamine D1 like and D2 like receptors using quantitative structure activity relationships (QSARs). Datasets of 29 and 69 molecules capable of binding to cloned human D1 and D2 receptors were ... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4121338 Mon, 25 Oct 2010 00:00:00 +0100 4121338 http://www.medworm.com/index.php?rid=4121337&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%3D20977415%26dopt%3DAbstract Authors: Deng XQ, Song MX, Wei CX, Li FN, Quan ZS The present study describes the chemical synthesis and anticonvulsant activity evaluation of a series of 7-alkoxy-triazolo-[3, 4-b]benzo[d]thiazoles. Most compounds exhibited good anticonvulsant activity in the Maximal electroshock (MES) test. And the structure-activity relationships (SAR) were analyzed. Among the compounds studied, 7-octyloxy-triazolo-[3, 4-b]benzo[d]thiazole (5g) was found to be the most potent compound with a median effective dose (ED(50)) value of 8.0 mg/kg and a protective index (PI) value of 15.0, possessing better anticonvulsant activity and higher safety than marketed drugs carbamazepine and phenytoin. The mechanism study of compound 5g showed that it displayed broad spectrum activity in several models, and it i... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4121337 Mon, 25 Oct 2010 00:00:00 +0100 4121337 http://www.medworm.com/index.php?rid=4121336&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%3D20977416%26dopt%3DAbstract Authors: Al-Shuneigat J, Yu JQ, Beale P, Fisher K, Huq F In this paper we report the synthesis and in vitro activity of two new mixed ligand platinum complexes: trans-[PtCl(2) (thiazole)(imidazole) [JH3] and trans-[PtCl(2) (thiazole)(3-hydroxypyridine) [JH4]. Although the compounds are less active than cisplatin against the parent ovarian cancer cell line A2780, they are more active than cisplatin against the resistant cell lines A2780(cisR) and A2780(ZD0473R), thus indicating that JH3 and JH4 have been better able to overcome mechanisms of resistance operating in A2780(cisR) and A2780(ZD0473R). When Pt-DNA binding levels at 24 h in A2780, A2780(cisR) and A2780(ZD0473R) cell lines are compared it is found that whereas for cisplatin the values in resistant cell lines are significantly l... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4121336 Mon, 25 Oct 2010 00:00:00 +0100 4121336 http://www.medworm.com/index.php?rid=4121335&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%3D20977417%26dopt%3DAbstract Authors: Mahipal , Tanwar OP, Karthikeyan C, Moorthy NS, Trivedi P The article describes the development of a robust pharmacophore model and the investigation of structure activity relationship analysis of 48 aminophenyl benzamide derivatives reported for Histone Deacetylase (HDAC) inhibition using PHASE module of Schrodinger software. A five point pharmacophore model consisting of two aromatic rings (R), two hydrogen bond donors (D) and one hydrogen bond acceptor (A) with discrete geometries as pharmacophoric features was developed and the generated pharmacophore model was used to derive a predictive atom-based 3D QSAR model for the studied dataset. The obtained 3D QSAR model has an excellent correlation coefficient value (r(2)=0.99) along with good statistical significance as shown b... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4121335 Mon, 25 Oct 2010 00:00:00 +0100 4121335 http://www.medworm.com/index.php?rid=4024928&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%3D20879977%26dopt%3DAbstract Authors: Wang B, Ge L, Huang W, Zhang H, Qian H, Li J, Zheng Y Recent studies indicated that andrographolide was a potential anti-HIV therapeutic agent. In the paper, the synthesis of a series of andrographolide derivatives was described and their anti-HIV activities were evaluated in vitro. As compared with TI, compounds 5c, 5d and 5i showed moderate inhibitory activities on the cytopathic effect with TI above 10. Among the derivatives, compound 5i was the best one with TI >51. PMID: 20879977 [PubMed - as supplied by publisher] (Source: Medicinal Chemistry) Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4024928 Tue, 28 Sep 2010 23:00:00 +0100 4024928 http://www.medworm.com/index.php?rid=4024927&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%3D20879978%26dopt%3DAbstract Authors: Ojo B, Chowdhury BK As part of a program to develop medications which can preferentially block the binding of cocaine to the dopamine transporter, yet spare dopamine, a new series of N-substituted methylphenidate derivatives was synthesized and evaluated for inhibitory potency in [[(3)H] WIN 35,428 binding and [[(3)H] dopamine uptake assays using rat striatal tissue. Structure-activity relationships studies associated these as potential cocaine antagonists were investigated. This series of methylphenidate analogs was developed by introducing various alkyl and aryl groups on the piperidine nitrogen. Preliminary pharmacological studies indicated that for the N-aryl group, the best activity is obtained when the piperidine nitrogen atom was alkylated with 4-chlorobenzyl group. The... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=4024927 Tue, 28 Sep 2010 23:00:00 +0100 4024927 http://www.medworm.com/index.php?rid=3981252&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%3D20843281%26dopt%3DAbstract Authors: Harpstrite SE, Prior JL, Sivapackiam J, Collins SD, Rath NP, Sharma V Zinc(II)complex (3) {bis(3-ethoxy-2-hydroxy-benzylidene)-N,N'-bis(2,2-dimethyl-3-aminopropyl)ethylenediamine}-zinc(II); [(3-OEt-ENBDMPI)Zn(II)] was obtained in situ by a ligand exchange reaction involving zinc(II) acetylacetonate and the Schiff-base ligand obtained in situ. For assessing ability of 3 to act as a transport substrate of multidrug resistance (MDR1) P-glycoprotein (Pgp), its cytotoxic activity was evaluated in human epidermal carcinoma drug-sensitive KB 3-1 (Pgp-) and drug resistant KB 8-5 (Pgp+) cells. Compared with its cationic gallium(III) counterpart 4 showing cytotoxicity profiles consistent with its recognition as a Pgp substrate, the neutral zinc(II) complex 3 did not display cytotoxicity... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=3981252 Mon, 13 Sep 2010 23:00:00 +0100 3981252 http://www.medworm.com/index.php?rid=3981251&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%3D20843282%26dopt%3DAbstract In this study we show that the cytotoxic effect of β-sitosterol was observed in both, estrogen-dependent and estrogen-independent cells. It was also shown that the β-sitosterol was significantly more cytotoxic in cells with basal ABCB1 expression (MCF7) than in multidrug resistant NCI/ADR-RES. Surprisingly, 5a,6a-epoxysitosterol did not decrease the viability of any investigated cells but on the contrary, it provoked their increased proliferation. It was shown that oxyphytosterols blocked the cell cycle of MCF7 cells in G0/G1 phase while did not affect NCI/ADR-RES cell cycle in physiological concentration range. We also show that PgP activity (responsible for Multidrug Resistance phenomena) is inhibited by β-sitosterol. Thus, the phytosterols are supposed to act at various mechani... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=3981251 Mon, 13 Sep 2010 23:00:00 +0100 3981251 http://www.medworm.com/index.php?rid=3981250&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%3D20843283%26dopt%3DAbstract Authors: Jacobsen S, Ostmann A Interactions between pharmaceutical ingredients play an important role in the development of drug formulations. It was the aim of our present studies to investigate drug-polymer interactions. Interaction of the antiviral drug acyclovir with polyethylenimines, polyvinylamines and the non-ionic PVP was investigated using a modified equilibrium dialysis. The membrane was only permeable to free acyclovir, while polymers and acyclovir-polymer-associates did not pass through. Significant amounts of acyclovir were bound with the polyethylenimines. The formation of associates consisting of acyclovir and either PVP or polyvinylamine could not be demonstrated. In solutions of acyclovir and polyethylenimine (Mr=25000) the amount of bound drug is increased with incre... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=3981250 Mon, 13 Sep 2010 23:00:00 +0100 3981250 http://www.medworm.com/index.php?rid=3981249&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%3D20843284%26dopt%3DAbstract Authors: Agrawal R, Thareja S, Rewatkar PV, Kokil GR, Verma A, Kalra A Oseltamivir (has known by its brand name 'Tamiflu') is a prodrug, requiring ester hydrolysis for conversion to the active form, Oseltamivir carboxylate. Oseltamivir was the first orally active neuraminidase inhibitor commercially developed by US based Gilead Sciences and is currently marketed by F. Hoffmann-La Roche (Roche). Oseltamivir is an antiviral drug which works by blocking the function of the viral neuraminidase protein. US FDA approved Oseltamivir for prophylaxis of uncomplicated influenza A and B. Currently, Oseltamivir is the only first line defense drug available for the treatment of Swine Flu. Orally Oseltamivir is well tolerated and effective in treatment of influenza in adolescents and adults, includi... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=3981249 Mon, 13 Sep 2010 23:00:00 +0100 3981249 http://www.medworm.com/index.php?rid=3981248&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%3D20843285%26dopt%3DAbstract Authors: Thareja S, Aggarwal S, Verma A, Bhardwaj TR, Kumara M A three-dimensional quantitative structure-activity relationship (3D-QSAR) study was performed on a series of 1, 3, 4-thiadiazole derivatives reported as anticonvulsant employing self-organizing molecular field analysis (SOMFA) techniques to investigate the structural requirements for the design of novel anticonvulsant. The training set composed of twenty two 1, 3, 4-thiadiazole derivatives that exhibit a potent activity in MMS test while predictive power was evaluated using a test set of 7 molecules. Physicochemical determinants of binding, such as steric and electrostatic properties, were mapped onto the molecular structures of 1, 3, 4-thiadiazole in order to interpret graphically the SOMFA results in terms of master grid... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=3981248 Mon, 13 Sep 2010 23:00:00 +0100 3981248 http://www.medworm.com/index.php?rid=3981247&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%3D20843286%26dopt%3DAbstract Conclusions: Subcutaneous administration of DHEA induced an increased survival rate and improved cellular immune functions in septic mice. In contrast, no comparable effects were noticed following intravenous or intraperitoneal administration of DHEA. PMID: 20843286 [PubMed - as supplied by publisher] (Source: Medicinal Chemistry) Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=3981247 Mon, 13 Sep 2010 23:00:00 +0100 3981247 http://www.medworm.com/index.php?rid=3981246&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%3D20843287%26dopt%3DAbstract Authors: Qian H, Fu Z, Huang W, Zhang H, Zhou J, Ge L, Lin R, Lin H, Hu X A series of capsaicin derivatives were designed and synthesized, including 10 compounds which are the combination of capsaicin and dihydro capsaicin with ibuprofen through bridge chain. Preliminary biological tests suggested that some compounds had both anti-inflammatory activity and analgesic activity. And their pungency was lower. Based on these results, some of these molecules can be considered as lead candidates for the further development of analgesic drugs. PMID: 20843287 [PubMed - as supplied by publisher] (Source: Medicinal Chemistry) Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=3981246 Mon, 13 Sep 2010 23:00:00 +0100 3981246 http://www.medworm.com/index.php?rid=3981245&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%3D20843288%26dopt%3DAbstract Authors: Mokale VJ, Raut MK, Burange PJ, Dhoot NS, Bhandari SV, Bothara KG, Naik JB Six derivatives of 1-(2-(benzoyl-(substituted)-2-phenyl-1H-indole-5-carbony) hydrazinyloxy) vinyl nitrate were synthesized and tested in vivo for anti-inflammatory, analgesic, and ulcerogenic properties. Synthesized compounds shown significant anti-inflammatory activity comparable to that of Diclofenac sodium in the carrageenan-induced rat paw edema test and all of the compounds were found to be equipotent to Diclofenac sodium in the acetic acid induced writhing analgesic model. Out of six derivatives two derivatives found to produce no ulceration in stomach specimen of rats; nitric oxide seems to contribute to their excellent safety profile which supports several endogenous GIT defense mechanisms, incl... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=3981245 Mon, 13 Sep 2010 23:00:00 +0100 3981245 http://www.medworm.com/index.php?rid=3981244&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%3D20843289%26dopt%3DAbstract We report here a new and more convergent synthetic pathway to amino side chain substituted hydantoins. Twenty new analogs of our lead compound were synthesized. None of them showed better in vitro affinity for σ(1) receptor than our lead compound. Nevertheless, three of them, obtained as racemates, showed high in vitro affinity and selectivity for σ(1) receptor. A preliminary in vivo evaluation of their pharmacological activity identified compound 22 as one that increases cocaine-induced locomotor stimulation and therefore acts as a potential efficient σ(1) agonist. PMID: 20843289 [PubMed - as supplied by publisher] (Source: Medicinal Chemistry) Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=3981244 Mon, 13 Sep 2010 23:00:00 +0100 3981244 http://www.medworm.com/index.php?rid=3981243&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%3D20843290%26dopt%3DAbstract Authors: García-Mayor RV, Larrañaga A Thionamide-derived antithyroid drugs (ATD) have been in use for over half a century and much is now known about their mechanism of action, pharmacokinetics and clinical pharmacology. Candidates for first option ATD therapy are young adults, without large goitre. The recommended initial dose for patients without big goitre and mild hyperthyroidism is 20 mg of MMI/CBZ. The recommended maintenance doses are 5-10 mg of MMI/CBZ. In cases of big goitre and/or severe hyperthyroidism the recommended initial dose is 30 to 40 mg/day. PTU use should be restricted to first trimester of pregnancy, doses should be as low as possible (150 to 200 mg/day) and then changing to MMI is recommended. Treatment Duration should be of 12-18 months. ATD plus thyroxine... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=3981243 Mon, 13 Sep 2010 23:00:00 +0100 3981243 http://www.medworm.com/index.php?rid=3764423&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%3D20632975%26dopt%3DAbstract Authors: Mitchell MO, Figliozzi RW, Guzel M Selective human butyrylcholinesterase (BChE) inhibitors such as cymserine have shown considerable promise for restoring cognition in Alzheimer's disease. Recently, (-)-debromoflustramine B, 1, a hexahydropyrrolo-[2,3-b]indole natural product isolated from the marine bryozoan Flustra foliacea, has demonstrated micromolar potency as a selective BChE inhibitor. Since (+/-)-demethyldebromoflustramine B, (+/-)-2, has an even lower IC(50), and the active enantiomer is (-)-2, derivatives of (-)-2 were constructed in silico and docked into the active site of BChE. Several compounds exhibited improved inhibitor potency and could be candidates for future synthesis and in vitro enzyme inhibition study. PMID: 20632975 [PubMed - as supplied by publish... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=3764423 Thu, 15 Jul 2010 23:00:00 +0100 3764423 http://www.medworm.com/index.php?rid=3764422&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%3D20632976%26dopt%3DAbstract Authors: Chavda S, Mulder K, Brown T, Mackay H, Babu B, Westrate L, Ferguson A, Lin S, Kiakos K, Ramos JP, Munde M, Wilson WD, Hartley JA, Lee M N-Methyl imidazole (Im) and N-methyl pyrrole (Py)-containing polyamides that can form stacked dimers can be programmed to target specific DNA sequences in the minor groove of DNA and control gene expression. Polyamides are being investigated as potential medicinal agents for treating diseases including cancer. The naturally occurring polyamide distamycin binds as a dimer in the minor groove of DNA and recognizes sequences rich in A/T and T/A base pairs indiscriminately. Synthetic analogs of distamycin that incorporate N-methylimidazole into the heterocyclic core have been shown to bind to G/C rich sequences with a high degree of specificity. T... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=3764422 Thu, 15 Jul 2010 23:00:00 +0100 3764422 http://www.medworm.com/index.php?rid=3764421&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%3D20632977%26dopt%3DAbstract In conclusion, phytochemical products and more specifically the isothiocyanates were effective inhibitors of the in vitro growth of the Gram-negative and Gram-positive pathogenic bacteria. Moreover, they can act synergistically with less efficient antibiotics to control bacterial growth. PMID: 20632977 [PubMed - as supplied by publisher] (Source: Medicinal Chemistry) Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=3764421 Thu, 15 Jul 2010 23:00:00 +0100 3764421 http://www.medworm.com/index.php?rid=3764420&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%3D20632978%26dopt%3DAbstract Authors: Semreen MH, El-Shorbagi AN, Al-Tel TH, Alsalahat IM The search for antiepileptic compounds with more selective activity continues to be an area of intensive investigation in medicinal chemistry. 3,5-Disubstituted tetrahydro-2H-1,3,5-thiadiazine-2-thione (THTT) derivatives, 3a-g, potential prodrugs incorporating the neurotransmitter GABA were synthesized and studied for crossing the blood-brain barrier (BBB). Compounds were prepared from primary amines and carbon disulfide to give dithiocarbamates 2a-g which upon reaction in situ with formaldehyde provided the intermediates Ia-g. Addition of Ia-g onto GABA furnished the title compounds 3a-g. The structures were verified by spectral data and the amounts of the compounds in the brain were investigated by using HPLC. The concentra... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=3764420 Thu, 15 Jul 2010 23:00:00 +0100 3764420 http://www.medworm.com/index.php?rid=3632942&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%3D20513223%26dopt%3DAbstract Authors: Bairwa R, Tawari NR, Alate A, Anam S, Degani MS, Ray MK, Rajan MG Siderophores are small molecules produced by bacteria under iron-scarcity conditions faced by bacteria inside host. Sideophores bind iron with high affinity (K(d) < 10(-25) M) and are required for iron transport into the bacterial cell. Small molecules interfering with siderophore functioning can be promising anti-mycobacterial agents. Several molecules with hydrazone as a structural feature are known to have metal chelating property. This prompted us to investigate the metal chelating ability of 2-hydrazino-pyrimidin-4(3H)-one derivatives. In this light, a library of 22 novel molecules with 2-hydrazino-pyrimidin-4(3H)-one moiety was synthesized and the compounds were evaluated against M. tuberculosis under i... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=3632942 Sun, 30 May 2010 23:00:00 +0100 3632942 http://www.medworm.com/index.php?rid=3614795&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%3D20507268%26dopt%3DAbstract Authors: Shen YZ, Ding YS, Gu Q, Chou KC The so-called "hub proteins" are those proteins in a protein-protein interaction network system that have remarkably higher interaction relations (or degrees) than the others. Therefore, the information of hub proteins can provide very useful insights for selecting or prioritizing targets during drug development. In this paper, by combining the multi-agent-based method with the graphical spectrum analysis and immune-genetic algorithm, a novel simulator for identifying the hub proteins from membrane protein interaction networks is proposed. As a demonstration of using the simulator, two hub membrane proteins, YPL227C and YIL147C, were identified from a complicated network system consisting of 1500 membrane proteins. Meanwhile, along with the two ... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=3614795 Thu, 27 May 2010 23:00:00 +0100 3614795 http://www.medworm.com/index.php?rid=3614794&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%3D20507269%26dopt%3DAbstract Authors: Nam NH, Dung PT, Thuong PT, Hien TT, Hieu DT A series of benzothiazole derivatives including N-(benzo[d]thiazol-2-yl)cyclohexanecarboxamides (2a-g) and N-(benzo[d]thiazol-2-yl)cyclohexancarbothioamides (3b-d) have been synthesized and evaluated for cytotoxic and antimicrobial activities. Two compounds including N-(6-ethoxybenzo[d]thiazol-2-yl)cyclohexanecarboxamide (2c) and N-(6-ethoxybenzo[d]thiazol-2-yl)cyclohexanecarbothiamide (3c) demonstrated significant cytotoxicity against three cancer cell lines (A549, MCF7-MDR and HT1080) while most of compounds exhibited moderate inhibitory effects on the growth of Staphyllococcus aureus and some other fungi. PMID: 20507269 [PubMed - as supplied by publisher] (Source: Medicinal Chemistry) Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=3614794 Thu, 27 May 2010 23:00:00 +0100 3614794 http://www.medworm.com/index.php?rid=3614793&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%3D20507270%26dopt%3DAbstract Authors: Ishimaru C, Takeuchi T, Sugawara F, Yoshida H, Mizushina Y This paper describes the inhibitory activities of diacylglyceride phospholipids, such as phosphatidylcholine (lecithin), phosphatidylethanolamine (cephalin), phosphatidylserine, phosphatidylglycerol, bisphosphatidylglycerol (cardiolipin), phosphatidylinositol, and phosphatidic acid (phosphatidate) (compounds 1 - 7, respectively) against DNA polymerase (pol), DNA topoisomerase (topo), and human cancer cell growth. Among the compounds tested, compounds 3 - 7 were revealed to be potent inhibitors of animal pols: compound 4 was the strongest inhibitor, with IC(50) values for different pols of 1.7 - 15 mM. Compounds 4 - 7 also inhibited the activity of human topo II: compound 7 was the strongest inhibitor, with an IC50 valu... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=3614793 Thu, 27 May 2010 23:00:00 +0100 3614793 http://www.medworm.com/index.php?rid=3538685&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%3D20438444%26dopt%3DAbstract We report herein the synthesis and biological evaluation of dimethyl-carbamic acid 2,3-bis-dimethylcarbamoyloxy-6-(4-ethyl-piperazine-1-carbonyl)-phenyl ester (SP-04), a new drug candidate that is designed to offer a multi-target therapeutic neuroprotective approach as a treatment for Alzheimer's disease (AD). SP-04 inhibits acetylcholinesterase (AchE) activity both in vitro and in vivo, and induces a dose-dependent increase in Ach levels. SP-04 releases the metabolite 4-(4-ethyl-piperazin-1-yl)-1-(2,3,4-trihydroxy-phenyl)-butan-1-one (SP-04m). Both SP-04 and SP-04m are s1-receptor antagonists supporting their interest in relieving symptoms related to psychosis, a non-cognitive condition often associated with AD. SP-04m displays important antioxidant properties and both SP-04 and SP-04m of... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=3538685 Tue, 04 May 2010 23:00:00 +0100 3538685 http://www.medworm.com/index.php?rid=3449275&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%3D20367615%26dopt%3DAbstract Authors: Bartzatt R, Cirillo SL, Cirillo JD Three derivatives of ciprofloxacin (compound B, C, and D) were constructed utilizing microwave synthesis methodology (compound D) or diazoalkane reaction in nonaqueous solvent (compounds B and C). The final structures of the derivatives featured an ester group in place of the original carboxyl group of the ciprofloxacin. These ester groups contained aliphatic single carbon (compound B), two carbon length (compound C), or three carbon length propyl ester group (compound D). The ester groups strongly affected the molecular properties of the parent ciprofloxacin. As the size of the ester group increased the formula weight, molar volume, and number of rotatable bonds increased. The Log P for these compounds were -0.701, -0.441, -0.065, 0.437 for ... Medicinal Chemistry journals http://www.medworm.com/rss/comments.php?id=3449275 Mon, 05 Apr 2010 23:00:00 +0100 3449275 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 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 the literature was documented. Overall it was found that drugs with the greatest tendency to induce neutrophil immaturity (chlorpromazine, clozapine and olanzapine) also showed the greatest tendency... 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