Deoxyribonucleoside 2′- or 3′-mixed disulfides: Prodrugs to target ribonucleotide reductase and/or to inhibit HIV reverse transcription

Abstract

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.