Are 5'-O-carbamate-2',3'-dideoxythiacytidine new anti-HIV and anti-HBV nucleoside drugs or prodrugs?
In contrast to 5'-O-carbonate 3TC derivatives (23, 24), which are clearly 3TC prodrugs, the corresponding 3TC carbamates (15-21 and 25), found to be very stable compounds with respect to enzymatic hydrolysis (cellular lysates and culture cell media) and still active on both HIV-1 and HBV infected cells, may not be 3TC prodrugs. The antiviral properties as well as the mechanism of action of 3TC analogues have been studied and evaluated.
Anastasi
Carole
C
Laboratoire de Chimie Biomoléculaire, INSERM U-382, IBDM, Université Méditerranée, Parc Scientifique de Luminy, 163 avenue de Luminy, case 901, 13288 Marseille Cedex 9, France.
Vlieghe
Patrick
P
Hantz
Olivier
O
Schorr
Olivier
O
Pannecouque
Christophe
C
Witvrouw
Myriam
M
De Clercq
Erik
E
Clayette
Pascal
P
Dereuddre-Bosquet
Nathalie
N
Dormont
Dominique
D
Gondois-Rey
Françoise
F
Hirsch
Ivan
I
Kraus
Jean-Louis
JL
D019380:Anti-HIV Agents / Q000378:metabolism / Q000494:pharmacology*; D000998:Antiviral Agents / Q000378:metabolism / Q000494:pharmacology*; D002460:Cell Line; D003470:Culture Media; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects; D006515:Hepatitis B virus / Q000187:drug effects*; D006801:Humans; D011355:Prodrugs / Q000378:metabolism / Q000494:pharmacology*
C482460:5'-O-carbamate-2',3'-dideoxythiacytidine; D019380:Anti-HIV Agents; D000998:Antiviral Agents; D003470:Culture Media; D011355:Prodrugs; D003841:Deoxycytidine