Synthesis, biological evaluation and molecular modeling of 2-Hydroxyisoquinoline-1,3-dione analogues as inhibitors of HIV reverse transcriptase associated ribonuclease H and polymerase

doi:10.1016/j.ejmech.2017.03.059

	Synthesis, biological evaluation and molecular modeling of 2-Hydroxyisoquinoline-1,3-dione analogues as inhibitors of HIV reverse transcriptase associated ribonuclease H and polymerase
	Tang, Jing 8; Vernekar, Sanjeev Kumar V.8; Chen, Yue-Lei1,8 ; Miller, Lena 7; Huber, Andrew D.5,6; Myshakina, Nataliya 4; Sarafianos, Stefan G.2,3,6; Parniak, Michael A.7; Wang, Zhengqiang 8
刊名	EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
	2017-06-16
卷号	133 页码:85-96
关键词	2-hydroxyisoquinoline-1,3-diones HIV RNase H Reverse transcriptase Inhibitor
ISSN号	0223-5234
DOI	10.1016/j.ejmech.2017.03.059
文献子类	Article
英文摘要	Human immunodeficiency virus (HIV) reverse transcriptase (RT) associated ribonuclease H (RNase H) remains the only virally encoded enzymatic function not clinically validated as an antiviral target. 2-Hydroxyisoquinoline-1,3-dione (HID) is known to confer active site directed inhibition of divalent metal-dependent enzymatic functions, such as HIV RNase H, integrase (IN) and hepatitis C virus (HCV) NS5B polymerase. We report herein the synthesis and biochemical evaluation of a few C-5, C-6 or C-7 substituted HID subtypes as HIV RNase H inhibitors. Our data indicate that while some of these subtypes inhibited both the RNase H and polymerase (pol) functions of RT, potent and selective RNase H inhibition was achieved with subtypes 8-9 as exemplified with compounds 8c and 9c. (C) 2017 Elsevier Masson SAS. All rights reserved.
资助项目	National Institutes of Health[AI100890] ; Research Development and Seed Grant Program of the Center for Drug Design, University of Minnesota[00000000]
WOS关键词	RNASE-H ; DRUG-RESISTANCE ; NONNUCLEOSIDE INHIBITOR ; DESIGN ; NUCLEOSIDE ; INTEGRASE ; COMPLEX ; NNRTIS ; VIRUS ; ASSAY
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
WOS记录号	WOS:000401388900008
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/272607]
专题	药物化学研究室
通讯作者	Wang, Zhengqiang
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Room 5407,555 Zuchongzhi Rd, Shanghai 201203, Peoples R China 2.Univ Missouri, Dept Biochem, Columbia, MO 65211 USA; 3.Univ Missouri, Dept Mol Microbiol & Immunol, Sch Med, Columbia, MO 65211 USA; 4.Chatham Univ, Dept Nat Sci, 1 Woodland Rd, Pittsburgh, PA 15232 USA; 5.Univ Missouri, Dept Vet Pathobiol, Columbia, MO 65211 USA; 6.Univ Missouri, Christopher S Bond Life Sci Ctr, Columbia, MO 65211 USA; 7.Univ Pittsburgh, Dept Microbiol & Mol Genet, Sch Med, Pittsburgh, PA 15219 USA; 8.Univ Minnesota, Acad Hlth Ctr, Ctr Drug Design, Minneapolis, MN 55455 USA;
推荐引用方式 GB/T 7714	Tang, Jing,Vernekar, Sanjeev Kumar V.,Chen, Yue-Lei,et al. Synthesis, biological evaluation and molecular modeling of 2-Hydroxyisoquinoline-1,3-dione analogues as inhibitors of HIV reverse transcriptase associated ribonuclease H and polymerase[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2017,133:85-96.
APA	Tang, Jing.,Vernekar, Sanjeev Kumar V..,Chen, Yue-Lei.,Miller, Lena.,Huber, Andrew D..,...&Wang, Zhengqiang.(2017).Synthesis, biological evaluation and molecular modeling of 2-Hydroxyisoquinoline-1,3-dione analogues as inhibitors of HIV reverse transcriptase associated ribonuclease H and polymerase.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,133,85-96.
MLA	Tang, Jing,et al."Synthesis, biological evaluation and molecular modeling of 2-Hydroxyisoquinoline-1,3-dione analogues as inhibitors of HIV reverse transcriptase associated ribonuclease H and polymerase".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 133(2017):85-96.