A new potential approach to block HIV-1 replication via protein-protein interaction and strand-transfer inhibition

Bioorg Med Chem. 2014 Apr 1;22(7):2269-79. doi: 10.1016/j.bmc.2014.02.012. Epub 2014 Feb 20.

Abstract

Therapeutic treatment of AIDS is recently characterized by a crescent effort towards the identification of multiple ligands able to target different steps of HIV-1 life cycle. Taking into consideration our previously obtained SAR information and combining some important chemical structural features we report herein the synthesis of novel benzyl-indole derivatives as anti-HIV agents. Through this work we identified new dual target small molecules able to inhibit both IN-LEDGF/p75 interaction and the IN strand-transfer step considered as two crucial phases of viral life cycle.

Keywords: Docking studies; Protein–protein interaction; Strand-transfer; Synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / chemical synthesis
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology*
  • Benzyl Compounds / chemical synthesis
  • Benzyl Compounds / chemistry
  • Benzyl Compounds / pharmacology
  • Dose-Response Relationship, Drug
  • HIV Integrase / metabolism*
  • HIV-1 / drug effects*
  • HIV-1 / physiology
  • Indoles / chemical synthesis
  • Indoles / chemistry
  • Indoles / pharmacology
  • Integrase Inhibitors / chemical synthesis
  • Integrase Inhibitors / chemistry
  • Integrase Inhibitors / pharmacology*
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Molecular Structure
  • Protein Binding / drug effects
  • Structure-Activity Relationship
  • Virus Replication / drug effects*

Substances

  • Anti-HIV Agents
  • Benzyl Compounds
  • Indoles
  • Integrase Inhibitors
  • Intercellular Signaling Peptides and Proteins
  • lens epithelium-derived growth factor
  • HIV Integrase