Identification of a series of novel derivatives as potent HCV inhibitors by a ligand-based virtual screening optimized procedure

Melagraki, G; Afantitis, A; Sarimveis, H; Koutentis, PA; Markopoulos, J; Igglessi-Markopoulou, O

dc.contributor.author	Melagraki, G	en
dc.contributor.author	Afantitis, A	en
dc.contributor.author	Sarimveis, H	en
dc.contributor.author	Koutentis, PA	en
dc.contributor.author	Markopoulos, J	en
dc.contributor.author	Igglessi-Markopoulou, O	en
dc.date.accessioned	2014-03-01T01:26:27Z
dc.date.available	2014-03-01T01:26:27Z
dc.date.issued	2007	en
dc.identifier.issn	0968-0896	en
dc.identifier.uri	https://dspace.lib.ntua.gr/xmlui/handle/123456789/18080
dc.subject	HCV	en
dc.subject	Ligand-based design	en
dc.subject	QSAR	en
dc.subject	Virtual screening	en
dc.subject.classification	Biochemistry & Molecular Biology	en
dc.subject.classification	Chemistry, Medicinal	en
dc.subject.classification	Chemistry, Organic	en
dc.subject.other	benzothiadiazine derivative	en
dc.subject.other	hepatitis c virus polymerase	en
dc.subject.other	n 1 (3 methylbutyl) 4 hydroxy 1,8 naphthyridon 3 yl benzothiadiazine derivative	en
dc.subject.other	n 1 benzyl	en
dc.subject.other	unclassified drug	en
dc.subject.other	virus enzyme	en
dc.subject.other	article	en
dc.subject.other	biological activity	en
dc.subject.other	controlled study	en
dc.subject.other	drug identification	en
dc.subject.other	drug potency	en
dc.subject.other	drug screening	en
dc.subject.other	enzyme activity	en
dc.subject.other	enzyme structure	en
dc.subject.other	gene insertion	en
dc.subject.other	genotype	en
dc.subject.other	nonhuman	en
dc.subject.other	pharmacophore	en
dc.subject.other	quantitative structure activity relation	en
dc.subject.other	virus inhibition	en
dc.subject.other	Benzothiadiazines	en
dc.subject.other	Computer Simulation	en
dc.subject.other	Databases, Factual	en
dc.subject.other	Drug Design	en
dc.subject.other	Enzyme Inhibitors	en
dc.subject.other	Inhibitory Concentration 50	en
dc.subject.other	Ligands	en
dc.subject.other	Linear Models	en
dc.subject.other	Microbial Sensitivity Tests	en
dc.subject.other	Molecular Structure	en
dc.subject.other	Quantitative Structure-Activity Relationship	en
dc.subject.other	Stereoisomerism	en
dc.subject.other	Viral Nonstructural Proteins	en
dc.subject.other	Hepatitis C virus	en
dc.title	Identification of a series of novel derivatives as potent HCV inhibitors by a ligand-based virtual screening optimized procedure	en
heal.type	journalArticle	en
heal.identifier.primary	10.1016/j.bmc.2007.08.036	en
heal.identifier.secondary	http://dx.doi.org/10.1016/j.bmc.2007.08.036	en
heal.language	English	en
heal.publicationDate	2007	en
heal.abstract	This paper presents the results of a ligand-based virtual screening optimized procedure on 98 compounds which have been recently evaluated as inhibitors of genotype 1 HCV polymerase. First, quantitative structure-activity patterns are investigated for the selected compounds and then structural modi. cations are proposed to afford novel active patterns. An accurate and reliable QSAR model involving five descriptors that is able to predict successfully the HCV inhibitory potency against genotype 1 HCV polymerase is presented. Furthermore, the effects of various structural modi. cations on biological activity are investigated and biological activities of novel structures are estimated using the developed QSAR model. More specifically a search for optimized pharmacophore patterns by insertions, substitutions, and ring fusions of pharmacophoric substituents of the main building block scaffolds is described. The detection of the domain of applicability defines compounds whose estimations can be accepted with confidence. (C) 2007 Elsevier Ltd. All rights reserved.	en
heal.publisher	PERGAMON-ELSEVIER SCIENCE LTD	en
heal.journalName	Bioorganic and Medicinal Chemistry	en
dc.identifier.doi	10.1016/j.bmc.2007.08.036	en
dc.identifier.isi	ISI:000253489100002	en
dc.identifier.volume	15	en
dc.identifier.issue	23	en
dc.identifier.spage	7237	en
dc.identifier.epage	7247	en