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 microM. All other tested human cell-lines displayed a far less antiproliferative sensitivity to FddThd, comparable with that of AzT.
Matthes
E
E
Central Institute of Molecular Biology, Academy of Sciences, GDR, Berlin-Buch.
Lehmann
C
C
Scholz
D
D
Rosenthal
H A
HA
Langen
P
P
D000818:Animals; D000998:Antiviral Agents; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D003565:Cytidine Diphosphate / Q000378:metabolism; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D015224:Dideoxynucleosides; D006678:HIV / Q000187:drug effects*; D006801:Humans; D051379:Mice; D010766:Phosphorylation; D051381:Rats; D013936:Thymidine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity; D014779:Virus Replication / Q000187:drug effects; D015215:Zidovudine
D000998:Antiviral Agents; D015224:Dideoxynucleosides; D015215:Zidovudine; D003565:Cytidine Diphosphate; C002854:alovudine; D013936:Thymidine