Cytostatic and antiherpesvirus type 1 and 2 activities of 1-beta-D-arabinofuranosylthymine (ara T) prodrugs.
A series of derivatives of the antibiotic 1-beta-D-arabinofuranosylthymine (ara T) was synthesized by esterification of the hydroxy group in the 5'-position of the arabinose moiety of the nucleoside with straight-chain and branched-chain carboxylic acids: acetyl-ara T, butyryl-ara T, valeroyl-ara T, pivaloyl-ara T and palmitoyl-ara T. These ara T prodrugs were evaluated for their effect on growth of L5178y mouse lymphoma cells and noninfected BHK-21 cells as well as for their antiviral activity in Herpes simplex virus type 1 and 2 infected BHK-21 cells. All compounds exhibited a marked antiherpes virus activity, whereas the cytostatic activity of two of them, the pivaleric ester and the palmitic ester, was extremely weak. The relative antiviral indices of the 5'-pivaloyl-ara T and 5'-palmitoyl-ara T were found to be much better than the index of ara T itself.
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001087:Arabinonucleosides / Q000138:chemical synthesis / Q000494:pharmacology*; D002460:Cell Line; D007940:Leukemia L5178 / Q000188:drug therapy; D051379:Mice; D018139:Simplexvirus / Q000187:drug effects*; D013936:Thymidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D001087:Arabinonucleosides; C010032:thymine arabinoside; D013936:Thymidine