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

Biochem Biophys Res Commun. 1988 Jun 16;153(2):825-31. doi: 10.1016/s0006-291x(88)81170-7.

Abstract

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 microM. All other tested human cell-lines displayed a far less antiproliferative sensitivity to FddThd, comparable with that of AzT.

MeSH terms

  • Animals
  • Antiviral Agents*
  • Cell Division / drug effects
  • Cell Line
  • Cell Survival / drug effects*
  • Cytidine Diphosphate / metabolism
  • Cytopathogenic Effect, Viral / drug effects
  • Dideoxynucleosides*
  • HIV / drug effects*
  • Humans
  • Mice
  • Phosphorylation
  • Rats
  • Thymidine / analogs & derivatives*
  • Thymidine / metabolism
  • Thymidine / pharmacology
  • Thymidine / toxicity
  • Virus Replication / drug effects
  • Zidovudine

Substances

  • Antiviral Agents
  • Dideoxynucleosides
  • Zidovudine
  • Cytidine Diphosphate
  • alovudine
  • Thymidine