Novel Pharmacophore Based Methods Reveal Gossypol as a Reverse Transcriptase Inhibitor

Authors

Paul A. Keller, University of WollongongFollow
C. Birch, Victorian Infectious Diseases Reference Laboratory
S. P. Leach, University of Wollongong
D. Tyssen, Victorian Infectious Diseases Laboratory
R. Griffith, University of Newcastle

RIS ID

10048

Publication Details

This article was originally published as: Keller, PA, Birch, C, Leach, SP, et al, Novel Pharmacophore Based Methods Reveal Gossypol as a Reverse Transcriptase Inhibitor, Journal of Molecular Graphics and Modelling, 2003, 21(5), 365-373. The journal homepage can be found here through Elsevier.

Abstract

In a program to identify new structural entities for the inhibition of the HIV-1 reverse transcriptase (RT) enzyme via database searching, a series of RT pharmacophores were developed. By utilising a novel filtering technique, the National Cancer Institute database of compounds was scanned producing 15 compounds to be screened for activity. A notable inclusion was a series of gossypol derivatives. The testing of a series of compounds revealed the parent compound gossypol to be an HIV-1 reverse transcriptase inhibitor. These results suggest that at least part of its anti-HIV activity is due to gossypol targeting the non-nucleoside inhibitor binding pocket of RT.