Pure nucleoside enantiomers of β-2',3'-dideoxycytidine analogs are selective inhibitors of hepatitis B virus in vitro

Abstract

(-)-β-L-2',3'-Dideoxycytidine (β-L-DDC), (+)-β-D-2',3'-dideoxycytidine (β-D-DDC), (-)-β-L-2',3'-dideoxy-5-fluorocytidine (β-L-FDDC), (-)-β-L- 2',3'-dideoxy-5-fluoro-3'-thiacytidine (β-L-FTC), and (+)-β-D-1,3- dioxolane-5-fluorocytidine (β-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 β-D-FDOC > β-L-FTC > β-L-FDDC ≃ β-L-DDC >> β-D-DDC. Inhibition of HBV in transfected liver cells by the cytosine nucleosides was selective. The β-L-nucleoside-5'-triphosphates were consistently more potent inhibitors of woodchuck hepatitis virus DNA polymerase than the corresponding natural β-D-enantiomers.