title: 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.
authors.affiliation: Institut de Biochimie Biophysique Moléculaire et Cellulaire, UMR 8619 CNRS, Université de Paris Sud, F-91405 Orsay, France. beatrice.roy@bbmpc.u-psud.fr
authors.forename: Béatrice
authors.initials: B
authors.lastname: Roy
authors.forename: Stéphane
authors.initials: S
authors.lastname: Chambert
authors.forename: Michel
authors.initials: M
authors.lastname: Lepoivre
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Aubertin
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Décout
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003853:Deoxyribonucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004220:Disulfides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects; D015498:HIV-2 / Q000187:drug effects; D006801:Humans; D051379:Mice; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors*; D018119:Stavudine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects
chemical_list: C475512:3'-deoxythymidin-3'-yl methyl disulfide; D019380:Anti-HIV Agents; D003853:Deoxyribonucleosides; D004220:Disulfides; D011355:Prodrugs; D018894:Reverse Transcriptase Inhibitors; D018119:Stavudine; D012264:Ribonucleotide Reductases