Identification of benzenesulfonamide quinoline derivatives as potent HIV-1 replication inhibitors targeting Rev protein

Org Biomol Chem. 2015 Feb 14;13(6):1792-9. doi: 10.1039/c4ob02247e.

Abstract

Human immunodeficiency virus type 1 (HIV-1) Rev protein facilitates the export of viral RNA from nucleus to cytoplasm, which is a key step in HIV-1 pathogenesis and transmission. In this study, we have screened a commercial library and identified the hit compound 1 bearing a benzenesulfonamide quinoline scaffold that inhibited Rev activity and HIV-1 infectivity. Compounds bearing this scaffold were synthesized and their SAR was studied. We identified compound 20 with low toxicity and potent activity to inhibit HIV-1 replication by affecting Rev function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / chemical synthesis
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology*
  • Benzene Derivatives / chemical synthesis
  • Benzene Derivatives / chemistry
  • Benzene Derivatives / pharmacology*
  • Gene Products, rev / antagonists & inhibitors*
  • Gene Products, rev / metabolism
  • HIV-1 / drug effects*
  • HIV-1 / growth & development
  • HIV-1 / metabolism
  • Molecular Structure
  • Quinolines / chemical synthesis
  • Quinolines / chemistry
  • Quinolines / pharmacology*
  • Sulfonamides / chemical synthesis
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacology*
  • Virus Replication / drug effects*

Substances

  • Anti-HIV Agents
  • Benzene Derivatives
  • Gene Products, rev
  • Quinolines
  • Sulfonamides