Pure nucleoside enantiomers of beta-2',3'-dideoxycytidine analogs are selective inhibitors of hepatitis B virus in vitro.
(-)-beta-L-2',3'-Dideoxycytidine (beta-L-DDC), (+)-beta-D-2',3'-dideoxycytidine (beta-D-DDC), (-)-beta-L-2',3'-dideoxy-5-fluorocytidine (beta-L-FDDC), (-)-beta-L-2',3'-dideoxy-5-fluoro-3'-thiacytidine (beta-L-FTC), and (+)-beta-D-1,3-dioxolane-5-fluorocytidine (beta-D-FDOC) were evaluated for their anti-hepatitis B virus (anti-HBV) activities in HBV-transfected human liver cells (2.2.15). The order of decreasing potency for the compounds at the 90% effect level was beta-D-FDOC > beta-L-FTC > beta-L-FDDC approximately beta-L-DDC >> beta-D-DDC. Inhibition of HBV in transfected liver cells by the cytosine nucleosides was selective. The beta-L-nucleoside-5'-triphosphates were consistently more potent inhibitors of woodchuck hepatitis virus DNA polymerase than the corresponding natural beta-D-enantiomers.
Schinazi
R F
RF
Georgia VA Research Center for AIDS and HIV Infections, Veterans Affairs Medical Center, Decatur 30033.
Gosselin
G
G
Faraj
A
A
Korba
B E
BE
Liotta
D C
DC
Chu
C K
CK
Mathé
C
C
Imbach
J L
JL
Sommadossi
J P
JP
D000998:Antiviral Agents / Q000494:pharmacology*; D017919:Hepatitis B Virus, Woodchuck / Q000201:enzymology; D006515:Hepatitis B virus / Q000187:drug effects*; D018197:Hepatoblastoma / Q000821:virology; D006801:Humans; D008113:Liver Neoplasms / Q000821:virology; D008826:Microbial Sensitivity Tests; D019384:Nucleic Acid Synthesis Inhibitors; D009705:Nucleosides / Q000494:pharmacology*; D013237:Stereoisomerism; D014162:Transfection; D014764:Viral Proteins / Q000037:antagonists & inhibitors; D016047:Zalcitabine / Q000031:analogs & derivatives*
D000998:Antiviral Agents; D019384:Nucleic Acid Synthesis Inhibitors; D009705:Nucleosides; D014764:Viral Proteins; D016047:Zalcitabine