Synthesis and biological evaluation of novel antiviral agents as protein-protein interaction inhibitors

J Enzyme Inhib Med Chem. 2014 Apr;29(2):237-42. doi: 10.3109/14756366.2013.766609. Epub 2013 Jul 16.

Abstract

In continuation of our research efforts toward the identification and optimization for novel inhibitors of interaction between human immunodeficiency virus type 1 integrase and cellular cofactor LEDGF/p75, we designed and synthesized a new series of 4-benzylindole derivatives. Most of the title compounds proved to be able to block this protein-protein interaction (PPI), with a percentage ranging from 30% to 90% at 100 µM. The most promising derivative was compound 10b showing IC50 value of 6.41 µM. The main structure-activity relationships (SAR) are discussed and rationalized by docking studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / chemical synthesis*
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology
  • Binding Sites
  • HIV Integrase / metabolism*
  • Indoles / chemical synthesis*
  • Indoles / chemistry
  • Indoles / pharmacology
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Molecular Docking Simulation
  • Molecular Structure
  • Protein Interaction Maps / drug effects*
  • Protein Structure, Tertiary

Substances

  • Anti-HIV Agents
  • Indoles
  • Intercellular Signaling Peptides and Proteins
  • lens epithelium-derived growth factor
  • HIV Integrase
  • p31 integrase protein, Human immunodeficiency virus 1