Logo image
Se connecter
Retour
Deoxyribonucleoside 2'- or 3'-mixed disulfides: prodrugs to target ribonucleotide reductase and/or to inhibit HIV reverse transcription
Article de revue   Avec comité de lecture

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

Béatrice Roy, Stéphane Chambert, Michel Lepoivre, Anne-Marie Aubertin, Jan Balzarini et Jean-Luc Décout
Journal of medicinal chemistry, Vol.46(13), pp.2565-2568
19/06/2003
DOI: https://doi.org/10.1021/jm0256225
PMID: 12801219

Résumé

Animals Anti-HIV Agents - chemical synthesis Anti-HIV Agents - chemistry Anti-HIV Agents - pharmacology Cell Division - drug effects Cells, Cultured Deoxyribonucleosides - chemical synthesis Deoxyribonucleosides - chemistry Deoxyribonucleosides - pharmacology Disulfides - chemical synthesis Disulfides - chemistry Disulfides - pharmacology HIV-1 - drug effects HIV-2 - drug effects Humans Mice Prodrugs - chemical synthesis Prodrugs - chemistry Prodrugs - pharmacology Reverse Transcriptase Inhibitors - chemical synthesis Reverse Transcriptase Inhibitors - chemistry Reverse Transcriptase Inhibitors - pharmacology Ribonucleotide Reductases - antagonists & inhibitors Stavudine - analogs & derivatives Stavudine - chemical synthesis Stavudine - chemistry Stavudine - pharmacology Structure-Activity Relationship T-Lymphocytes - cytology T-Lymphocytes - drug effects
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.

Indicateurs

1 Consultations de la notice

Détails

Logo image