Computational strategies in discovering novel non-nucleoside inhibitors of HIV-1 RT

  • J Med Chem. 2005 May 5;48(9):3433-7. doi: 10.1021/jm049279a.
Maria Letizia Barreca  1 ,  Angela Rao ,  Laura De Luca ,  Maria Zappalà ,  Anna-Maria Monforte ,  Giovanni Maga ,  Christophe Pannecouque ,  Jan Balzarini ,  Erik De Clercq ,  Alba Chimirri ,  Pietro Monforte
Affiliations
  • 1. Dipartimento Farmaco-Chimico, Università di Messina, Viale Annunziata, 98168 Messina, Italy. barreca@ pharma.unime.it
PMID: 15857150 DOI: 10.1021/jm049279a
Abstract

A three-dimensional common feature pharmacophore model was developed using the X-ray structure of RT/non-nucleoside inhibitor (NNRTI) complexes. Starting from the pharmacophore hypothesis and the structure of the lead compound TBZ, new NNRTIs were designed and synthesized, having the benzimidazol-2-one system as a scaffold. Docking experiments showed that these molecules docked in a position and orientation similar to that of known inhibitors. Biological testing confirmed that our strategy was successful in searching for new leads as NNRTIs.