Development of a series of 3-hydroxyquinolin-2(1H)-ones as selective inhibitors of HIV-1 reverse transcriptase associated RNase H activity

Bioorg Med Chem Lett. 2012 Jun 15;22(12):3988-92. doi: 10.1016/j.bmcl.2012.04.096. Epub 2012 Apr 30.

Abstract

We report herein the synthesis of a series of 3-hydroxyquinolin-2(1H)-one derivatives. Esters and amide groups were introduced at position 4 of the basis scaffold and some modulations of the benzenic moiety were performed. Most compounds presented selective inhibitory properties in the 10-20 μM range against HIV-1 reverse transcriptase associated ribonuclease H activity, without affecting the integrase and reverse transcriptase DNA polymerase activities. Unfortunately all tested compounds exhibited high cellular cytotoxicity in cell culture which limited their applications as antiviral agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / chemical synthesis*
  • Anti-HIV Agents / pharmacology
  • Cell Line
  • Cell Survival / drug effects
  • Fluorescence
  • HIV Reverse Transcriptase / antagonists & inhibitors*
  • HIV Reverse Transcriptase / metabolism
  • HIV-1 / drug effects
  • HIV-1 / enzymology
  • Humans
  • Magnesium / chemistry
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Quinolones / chemical synthesis*
  • Quinolones / pharmacology
  • Reverse Transcriptase Inhibitors / chemical synthesis*
  • Reverse Transcriptase Inhibitors / pharmacology
  • Ribonuclease H, Human Immunodeficiency Virus / antagonists & inhibitors*
  • Ribonuclease H, Human Immunodeficiency Virus / metabolism
  • Spectrometry, Fluorescence
  • Structure-Activity Relationship

Substances

  • Anti-HIV Agents
  • Quinolones
  • Reverse Transcriptase Inhibitors
  • reverse transcriptase, Human immunodeficiency virus 1
  • HIV Reverse Transcriptase
  • Ribonuclease H, Human Immunodeficiency Virus
  • Magnesium