New chloro,fluorobenzylindole derivatives as integrase strand-transfer inhibitors (INSTIs) and their mode of action

Bioorg Med Chem. 2010 Aug 1;18(15):5510-8. doi: 10.1016/j.bmc.2010.06.063. Epub 2010 Jun 22.

Abstract

The life cycle of HIV-1 requires extensive assistance from the integrase (IN) enzyme which therefore constitutes an attractive therapeutic target for the development of anti-AIDS agents. We herein report the synthesis and biological evaluation of new HIV integrase strand-transfer inhibitors (INSTIs) which proved to be also potent anti-HIV agents. The binding mode of the most representative molecules were also studied by induced-fit docking (IFD). The obtained IFD results were consistent with the mechanism of action proposed for this class of IN inhibitors, that is metal chelating/binding agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Cell Line
  • Computer Simulation
  • HIV Integrase / chemistry*
  • HIV Integrase / metabolism
  • HIV Integrase Inhibitors / chemical synthesis
  • HIV Integrase Inhibitors / chemistry*
  • HIV Integrase Inhibitors / pharmacology
  • Humans
  • Indoles / chemical synthesis
  • Indoles / chemistry*
  • Indoles / pharmacology
  • Models, Molecular

Substances

  • HIV Integrase Inhibitors
  • Indoles
  • HIV Integrase