Title: Synthesis and HIV-1 RT inhibitory action of novel (4/6-substituted benzo[d]thiazol -2-yl)thiazolidin-4-ones. Divergence from the non-competitive inhibition mechanism
Authors: Pitta, Eleni ×
Geronikaki, Athina
Surmava, Sofiko
Eleftheriou, Phaedra
Mehta, Vaibhav P
Van der Eycken, Erik #
Issue Date: 2013
Publisher: Taylor & Francis
Series Title: Journal of enzyme inhibition and medicinal chemistry vol:28 issue:1 pages:113-122
Abstract: Reverse transcriptase (RT) inhibitors play a major role in the therapy of human immunodeficiency virus type 1 (HIV-1) infection. Although, many compounds are already used as anti-HIV drugs, research on development of novel inhibitors continues, since drug resistant strains appear because of prolonged therapy. In this paper, we present the synthesis and evaluation of HIV-1 RT inhibitory action of eighteen novel (4/6-halogen/MeO/EtO-substituted benzo[d]thiazol-2-yl)thiazolidin-4-ones. The two more active compounds (IC50 : 0.04 µM and 0.25 µM) exhibited better inhibitory action than the reference compound, nevirapine. Docking analysis supports a stable binding of the most active derivative to the allosteric centre of RT. Kinetic analysis of two of the most active compounds indicate an uncompetitive inhibition mode. This is a desired characteristic, since mutations that affect activity of traditional non-competitive NNRTIs may not affect activity of compounds of this series. Interestingly, the less active derivatives (IC50 > 40 µM) exhibit a competitive mode of action.
ISSN: 1475-6366
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular Design and Synthesis
× corresponding author
# (joint) last author

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