Synthesis, biological evaluation and molecular modeling studies of quinolonyl diketo acid derivatives: new structural insight into the HIV-1 integrase inhibition

Eur J Med Chem. 2011 May;46(5):1749-56. doi: 10.1016/j.ejmech.2011.02.028. Epub 2011 Feb 22.

Abstract

New quinolonyl diketo acid compounds bearing various substituents at position 6 of the quinolone scaffold were designed and synthesized as potential HIV-1 integrase inhibitors. These new compounds were evaluated for their antiviral and anti-integrase activity and showed inhibitory potency similar to that of 6-bromide analog 2. Molecular modeling and docking studies were performed to rationalize these data and to provide a detailed understanding of the mechanism of inhibition for this class of compounds.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / chemical synthesis
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology*
  • Catalytic Domain / drug effects
  • Dose-Response Relationship, Drug
  • Drug Design
  • HIV / drug effects*
  • HIV Integrase / chemistry
  • HIV Integrase / metabolism*
  • HIV Integrase Inhibitors / chemical synthesis
  • HIV Integrase Inhibitors / chemistry
  • HIV Integrase Inhibitors / pharmacology*
  • Keto Acids / chemical synthesis
  • Keto Acids / chemistry
  • Keto Acids / pharmacology*
  • Models, Molecular
  • Molecular Structure
  • Quinolones / chemical synthesis
  • Quinolones / chemistry
  • Quinolones / pharmacology*
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Anti-HIV Agents
  • HIV Integrase Inhibitors
  • Keto Acids
  • Quinolones
  • HIV Integrase