Synthesis of 5-haloethynyl- and 5-(1,2-dihalo)vinyluracil nucleosides: antiviral activity and cellular toxicity.
In this article, we report the synthesis of hitherto unknown 5-haloethynyl and 5-(1,2-dihalo)vinyluracil nucleosides in the 2'-deoxy, 3'-deoxy- and ribosyl series, and we discuss their in vitro anti-HIV and anti-HCV activities and cellular toxicitites. As a result, on the basis of their selectivity index (SI) obtained with the HCV replicon system, but also on their cytotoxicity on peripheral blood mononuclear, CEM and VERO cell lines, the best compounds were the 5-bromoethynyluridine (SI = 3.2) and the 5-(1-chloro-2-iodo)vinyluridine (SI > 2.8).
Escuret
Vanessa
V
Institut de Chimie Organique et Analytique, ICOA UMR 6005, UFR Sciences, BP 6759, 45067 Orléans Cedex 2, France.
Aucagne
Vincent
V
Joubert
Nicolas
N
Durantel
David
D
Rapp
Kimberly L
KL
Schinazi
Raymond F
RF
Zoulim
Fabien
F
Agrofoglio
Luigi A
LA
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006678:HIV / Q000187:drug effects / Q000502:physiology; D016174:Hepacivirus / Q000187:drug effects / Q000502:physiology; D015394:Molecular Structure; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D013329:Structure-Activity Relationship; D014498:Uracil / Q000737:chemistry*
D000998:Antiviral Agents; D009705:Nucleosides; D014498:Uracil