Insight into the Structural Requirements of Benzothiadiazine Scaffold-Based Derivatives as Hepatitis C Virus NS5B Polymerase Inhibitors Using 3D-QSAR, Molecular Docking and Molecular Dynamics
文献类型：期刊论文
| 作者 | Zhang, H-X.1; Li, Y.1; Wang, X.2; Xiao, Z-T.2; Wang, Y-H.2,3 |
| 刊名 | current medicinal chemistry
 |
| 出版日期 | 2011-09-01 |
| 卷号 | 18期号:26页码:4019-4028 |
| 关键词 | HCV NS5B benzothiadiazine scaffold-based inhibitors 3D-QSAR CoMFA CoMSIA molecular docking molecular dynamics |
| 英文摘要 | hepatitis c virus (hcv) infection is a significant world health threat with frequently ineffective problem existed in the present treatment, thus representing a major unmet medical need. the nonstructural viral protein 5b (ns5b), one of the best-studied polymerase, has emerged as an attractive target for the development of novel therapeutics against hepatitis c virus. in this work, both ligand-and receptor-based three-dimensional quantitative structure-activity relationship (3d-qsar) studies were carried out using comparative molecular field analysis (comfa) and comparative molecular similarity indices analysis (comsia) techniques on 360 benzothiadiazine scaffold-based derivatives as hcv gt-1b ns5b polymerase allosteric inhibitors. the resultant optimum 3d-qsar model exhibited r(cv)(2) of 0.54, r(ncv)(2) of 0.72 and the predictive ability was validated by using an independent test set of 90 compounds which gave r(pred)(2) value of 0.64. in addition, docking analysis and molecular dynamics simulation (md) were also applied to elucidate the probable binding modes of these inhibitors at the allosteric site of the enzyme. interpretation of the 3d contour maps in context of the topology of the allosteric binding site of ns5b provided insight into ns5b-inhibitor interactions. the information obtained from this work can be utilized to accurately predict the binding affinity of related analogues and also facilitate the future rational design of novel inhibitors with improved activity. |
| WOS标题词 | science & technology ; life sciences & biomedicine |
| 类目[WOS] | biochemistry & molecular biology ; chemistry, medicinal ; pharmacology & pharmacy |
| 研究领域[WOS] | biochemistry & molecular biology ; pharmacology & pharmacy |
| 关键词[WOS] | dependent rna-polymerase ; field analysis comfa ; hcvns5b polymerase ; nonnucleoside inhibitors ; part 1 ; allosteric inhibitors ; similarity indexes ; viral-hepatitis ; analysis comsia ; plus ribavirin |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000294901100009 |
| 公开日期 | 2015-11-17 |
| 源URL | [http://159.226.238.44/handle/321008/142650]  |
| 专题 | 大连化学物理研究所_中国科学院大连化学物理研究所 |
| 作者单位 | 1.Dalian Univ Technol, Sch Chem Engn, Dalian 116024, Liaoning, Peoples R China 2.NW A&F Univ, Ctr Bioinformat, Yangling 712100, Shaanxi, Peoples R China 3.Chinese Acad Sci, Lab Pharmaceut Resource Discovery, Dalian Inst Chem Phys, Dalian 116023, Liaoning, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhang, H-X.,Li, Y.,Wang, X.,et al. Insight into the Structural Requirements of Benzothiadiazine Scaffold-Based Derivatives as Hepatitis C Virus NS5B Polymerase Inhibitors Using 3D-QSAR, Molecular Docking and Molecular Dynamics[J]. current medicinal chemistry,2011,18(26):4019-4028. |
| APA | Zhang, H-X.,Li, Y.,Wang, X.,Xiao, Z-T.,&Wang, Y-H..(2011).Insight into the Structural Requirements of Benzothiadiazine Scaffold-Based Derivatives as Hepatitis C Virus NS5B Polymerase Inhibitors Using 3D-QSAR, Molecular Docking and Molecular Dynamics.current medicinal chemistry,18(26),4019-4028. |
| MLA | Zhang, H-X.,et al."Insight into the Structural Requirements of Benzothiadiazine Scaffold-Based Derivatives as Hepatitis C Virus NS5B Polymerase Inhibitors Using 3D-QSAR, Molecular Docking and Molecular Dynamics".current medicinal chemistry 18.26(2011):4019-4028. |
入库方式： OAI收割
来源：大连化学物理研究所
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