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.
Stefania Ferro  1 ,  Laura De Luca ,  Maria Letizia Barreca ,  Sara De Grazia ,  Frauke Christ ,  Zeger Debyser ,  Alba Chimirri
Affiliations
  • 1. Dipartimento Farmaco-Chimico, Università di Messina, Viale Annunziata, I-98168 Messina, Italy.
PMID: 20630765 DOI: 10.1016/j.bmc.2010.06.063
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.