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

Bioorg Med Chem Lett. 2019 Dec 15;29(24):126638. doi: 10.1016/j.bmcl.2019.126638. Epub 2019 Aug 28.

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.

Keywords: Antiviral activity; Molecular docking; Optimization; Structure-activity relationship; Vif inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzamides / chemical synthesis*
  • Benzamides / chemistry
  • HIV-1 / drug effects*
  • Structure-Activity Relationship
  • vif Gene Products, Human Immunodeficiency Virus / antagonists & inhibitors*

Substances

  • Benzamides
  • vif Gene Products, Human Immunodeficiency Virus