Synthesis cytostatic and anti-HIV evaluations of the new unsaturated acyclic C-5 pyrimidine nucleoside analogues

摘要

A series of the novel C-5 alkynyl pyrimidine nucleoside analogues ( – ) in which the sugar moiety was replaced by the conformationally restricted - and -2-butenyl spacer between the phthalimido and pyrimidine ring were synthesized by using Sonogashira cross-coupling reaction. Cytostatic activity evaluation of the novel compounds showed that -isomers exhibited, in general, better cytostatic activities than the corresponding -isomers. -isomer exhibited the best cytostatic effect against all evaluated malignant cell lines, particularly against hepatocellular carcinoma (Hep G2, IC  = 4.3 μM). However, this compound was also cytotoxic to human normal fibroblasts (WI 38). Its -isomer showed highly specific antiproliferative activity against Hep G2 (IC  = 18 μM) and no cytotoxicity to WI 38. Moreover, compounds , and expressed some marginal inhibitory activity against HIV-1 and HIV-2.