Studies of Benzothiadiazine Derivatives as Hepatitis C Virus NS5B Polymerase Inhibitors Using 3D-QSAR, Molecular Docking and Molecular Dynamics

	Studies of Benzothiadiazine Derivatives as Hepatitis C Virus NS5B Polymerase Inhibitors Using 3D-QSAR, Molecular Docking and Molecular Dynamics
	Wang, X.1; Yang, W.1; Xu, X.1; Zhang, H.1; Li, Y.2; Wang, Y.1,3
刊名	current medicinal chemistry
	2010-09-01
卷号	17 期号:25 页码:2788-2803
关键词	HCV NS5B benzothiadiazine analogs allosteric site 3D-QSAR CoMFA CoMSIA molecular docking molecular dynamics
英文摘要	in order to explore the structure-activity correlation of benzothiadiazine series as inhibitors of genotype 1a hcv polymerase, a set of ligand-and receptor-based 3d-qsar models were, for the first time, developed in the present work employing comparative molecular field analysis (comfa) and comparative molecular similarity index analysis (comsia) for 239 promising molecules. in addition, homology modeling, 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. the statistical model validations assure the reliability of the obtained qsar models. changes in the binding affinity of the inhibitors attributing to modifications in the aromatic rings could be rationalized by the steric, electrostatic, hydrophobic, and hydrogen bond acceptor properties. (i) hydrophobic substituents with similar size of benzo group like isosteres are preferential at positions 1 and 2 (ring b of benzothiadiazines). (ii) substituents at position-3 containing a linear alkyl chain (four or five carbon atoms) or a branched alkyl chain (five-eight carbons) can increase the inhibitory activity by one to two orders of magnitude. (iii) a polar substituent like methanesulfonamide group at position-14 can enhance the activity of the drug by providing a hydrogen bonding interaction with the protein target. the results obtained from this work provide important guidelines in design of novel benzothiadiazine analogs as inhibitors of hcv genotype 1a ns5b.
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 ; similarity indexes analysis ; nonstructural protein 5b ; field analysis comfa ; hcvns5b polymerase ; nonnucleoside inhibitors ; 3d qsar ; crystal-structures ; analysis comsia ; swiss-model
收录类别	SCI
语种	英语
WOS记录号	WOS:000280507600008
公开日期	2015-11-17
内容类型	期刊论文
源URL	[http://159.226.238.44/handle/321008/142150]
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.NW A&F Univ, Ctr Bioinformat, Yangling 712100, Shaanxi, Peoples R China 2.Dalian Univ Technol, Sch Chem Engn, Dalian 116012, Liaoning, Peoples R China 3.Chinese Acad Sci, Dalian Inst Chem Phys, Lab Pharmaceut Resource Discovery, Grad Sch, Dalian 116023, Liaoning, Peoples R China
推荐引用方式 GB/T 7714	Wang, X.,Yang, W.,Xu, X.,et al. Studies of Benzothiadiazine Derivatives as Hepatitis C Virus NS5B Polymerase Inhibitors Using 3D-QSAR, Molecular Docking and Molecular Dynamics[J]. current medicinal chemistry,2010,17(25):2788-2803.
APA	Wang, X.,Yang, W.,Xu, X.,Zhang, H.,Li, Y.,&Wang, Y..(2010).Studies of Benzothiadiazine Derivatives as Hepatitis C Virus NS5B Polymerase Inhibitors Using 3D-QSAR, Molecular Docking and Molecular Dynamics.current medicinal chemistry,17(25),2788-2803.
MLA	Wang, X.,et al."Studies of Benzothiadiazine Derivatives as Hepatitis C Virus NS5B Polymerase Inhibitors Using 3D-QSAR, Molecular Docking and Molecular Dynamics".current medicinal chemistry 17.25(2010):2788-2803.