Phosphorylation, anti-HIV activity and cytotoxicity of 3′-fluorothymidine

3′-fluorothymidine (FddThd) is well phosphorylated to the 5′-triphosphate in various relevant cell-lines. This results in fairly stable levels of this compound without accumulation of the 5′-monophosphate to the extent described for 3′-azidothymidine (AzT). The di- and triphosphate of FddThd seems unable to influence the ribonucleotide reductase in permeable cells. FddThd protects 50% of the MT-4 cells against the cytopathic effect of HIV at 3 nM, but reduces the number of uninfected viable cells to 50% at 1.1 μM. All other tested human cell-lines displayed a far less antiproliferative sensitivity to FddThd, comparable with that of AzT.