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Updated: Jun 8, 2026

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
Toward the first nonpeptidic molecular tong inhibitor of wild-type and mutated HIV-1 protease dimerization
Anamaria Vidu1, Laure Dufau, Ludovic Bannwarth
1Molécules Fluorées et Chimie Médicinale, BioCIS UMR-CNRS 8076, IPSIT, Université Paris-Sud 11, Faculté de Pharmacie, 5 rue Jean-Baptiste Clément, 92296, Châtenay-Malabry Cedex, France.
Abstract:
Herein we describe the synthesis and HIV-1 protease (PR) inhibitory activity of 16 new peptidomimetic molecular tongs with a naphthalene scaffold. Their peptidic character was progressively decreased. Two of these molecules exhibited the best dimerization inhibition activity toward HIV-1 wild-type and multimutated ANAM-11 proteases obtained to date for this class of molecules (∼40 nM for wild-type PR and 100 nM for ANAM-11 PR). Although the peptidic character of one molecular tong was completely suppressed, the mechanism of inhibition and inhibitory potency toward both proteases were maintained.
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