Author:

Keywords:

Animals, Anti-HIV Agents, Cell Division, Cells, Cultured, Deoxyribonucleosides, Disulfides, HIV-1, HIV-2, Humans, Mice, Prodrugs, Reverse Transcriptase Inhibitors, Ribonucleotide Reductases, Stavudine, Structure-Activity Relationship, T-Lymphocytes, Science & Technology, Life Sciences & Biomedicine, Chemistry, Medicinal, Pharmacology & Pharmacy, BIOLOGICAL APPLICATIONS, NUCLEOSIDE CHEMISTRY, DNA-SYNTHESIS, HYDROXYUREA, DERIVATIVES, PYRIMIDINE, SUGAR, 0304 Medicinal and Biomolecular Chemistry, 0305 Organic Chemistry, 1115 Pharmacology and Pharmaceutical Sciences, Medicinal & Biomolecular Chemistry, 3214 Pharmacology and pharmaceutical sciences, 3404 Medicinal and biomolecular chemistry, 3405 Organic chemistry

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.