Design, synthesis, and biological evaluation of 2-amino-N-(2-methoxyphenyl)-6-((4-nitrophenyl)sulfonyl)benzamide derivatives as potent HIV-1 Vif inhibitors.

Abstract:

:Viral infectivity factor (Vif) is one of the accessory protein of human immunodeficiency virus type I (HIV-1) that inhibits host defense factor, APOBEC3G (A3G), mediated viral cDNA hypermutations. Previous work developed a novel Vif inhibitor 2-amino-N-(2-methoxyphenyl)-6-((4-nitrophenyl)thio)benzamide (1) with strong antiviral activity. Through optimizations on the two side branches, a series of compound 1 derivatives (2-18) were designed, synthesized and tested in vitro for their antiviral activities. The biological results showed that compound 5 and 16 inhibited the virus replication efficiently with EC50 values of 9.81 and 4.62 μM. Meanwhile, low cytotoxicities on H9 cells were observed for the generated compounds by the MTT assay. The structure-activity relationship of compound 1 was preliminarily clarified, which gave rise to the development of more potent Vif inhibitors.

journal_name

Bioorg Med Chem Lett

authors

Zhang RH,Wang S,Luo RH,Zhou M,Zhang H,Xu GB,Zhao YL,Li YJ,Wang YL,Yan G,Liao SG,Zheng YT,Li R

doi

10.1016/j.bmcl.2019.126638

subject

Has Abstract

pub_date

2019-12-15 00:00:00

pages

126638

issue

24

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(19)30583-9

journal_volume

29

pub_type

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