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Updated: Jul 4, 2026

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
Anti-retroviral and cytostatic activity of 2',3'-dideoxyribonucleoside 3'-disulfides
Béatrice Gerland1, Jérôme Désiré, Jan Balzarini
1Université de Grenoble/CNRS, UMR 5063, Département de Pharmacochimie Moléculaire, ICMG FR 2607, BP 53 F-38041 Grenoble Cedex 9, France.
Abstract:
Herein, we report the synthesis, antiviral and cytostatic effects of nucleosides bearing a 3'-disulfide function as prodrugs of potentially active 3'-mercaptonucleotides. The lack of the anti-HIV effects in mutant CEM/TK-cells for most of the thymidine disulfides suggests that a phosphorylation step involving thymidine kinase is necessary for the eventual antiviral activity of the thymidine nucleosides. The comparable anti-HIV activities of most of the disulfides and their rapid reduction in CEM cell extracts imply an inhibitory effect of the 2',3'-dideoxy-3'-mercaptothymidine 5'-triphosphate metabolite. The cytostatic effects of the disulfides in CEM/0 and Molt4/C8 cells appeared to be strongly dependent on the nature of the non-nucleosidic disulfide moiety and were decreased in preserving the anti-retroviral activity.
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