2-Aminothiazolones as anti-HIV agents that act as gp120-CD4 inhibitors

Antimicrob Agents Chemother. 2014 Jun;58(6):3043-52. doi: 10.1128/AAC.02739-13. Epub 2014 Mar 10.

Abstract

We report here the synthesis of 2-aminothiazolones along with their biological properties as novel anti-HIV agents. Such compounds have proven to act through the inhibition of the gp120-CD4 protein-protein interaction that occurs at the very early stage of the HIV-1 entry process. No cytotoxicity was found for these compounds, and broad antiviral activities against laboratory strains and pseudotyped viruses were documented. Docking simulations have also been applied to predict the mechanism, at the molecular level, by which the inhibitors were able to interact within the Phe43 cavity of HIV-1 gp120. Furthermore, a preliminary absorption, distribution, metabolism, and excretion (ADME) evaluation was performed. Overall, this study led the basis for the development of more potent HIV entry inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology*
  • CD4 Antigens / chemistry
  • CD4 Antigens / drug effects*
  • CD4 Antigens / metabolism
  • Cell Line
  • HIV Envelope Protein gp120 / antagonists & inhibitors*
  • HIV Envelope Protein gp120 / metabolism
  • HIV Fusion Inhibitors / chemistry
  • HIV Fusion Inhibitors / pharmacology*
  • HIV-1 / drug effects*
  • Humans
  • Molecular Docking Simulation
  • Protein Binding

Substances

  • Anti-HIV Agents
  • CD4 Antigens
  • HIV Envelope Protein gp120
  • HIV Fusion Inhibitors

Associated data

  • PDB/1G9M
  • PDB/2B4C
  • PDB/3TGS
  • PDB/4I54