Deoxyribonucleoside 2'- or 3'-mixed disulfides: prodrugs to target ribonucleotide reductase and/or to inhibit HIV reverse transcription
Roy, Béatrice × Chambert, Stéphane Lepoivre, Michel Aubertin, Anne-Marie Balzarini, Jan Décout, Jean-Luc #
Journal of Medicinal Chemistry vol:46 issue:13 pages:2565-8
Herein, we report the design, synthesis, and biological effects of nucleosides bearing a disulfide function on the sugar ring as prodrugs of potentially active mercaptonucleotides that can target ribonucleotide reductase or reverse transcriptase. We show that cytidine derivatives efficiently reduce dNTP pools in human CEM/SS cells and that 3'-deoxythymidin-3'-yl methyl disulfide is able to interfere with both cellular dNTP synthesis and HIV reverse transcription.