Novel pharmacophore-based methods reveal gossypol as a reverse transcriptase inhibitor.
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 a part of its anti-HIV activity is due to gossypol targeting the non-nucleoside inhibitor binding pocket of RT.
Keller
Paul A
PA
Department of Chemistry, University of Wollongong, Wollongong, NSW 2522, Australia. paul.keller@uow.edu.au
Birch
Chris
C
Leach
Scott P
SP
Tyssen
David
D
Griffith
Renate
R
D016208:Databases, Factual; D006072:Gossypol / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D015394:Molecular Structure; D019829:Nevirapine / Q000737:chemistry; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D012984:Software
D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine; D054303:HIV Reverse Transcriptase; D006072:Gossypol