Antitumor activity of sugar-modified cytosine nucleosides.

摘要: Nucleoside analogues which show antimetabolic activity in cells have been successfully used the treatment of various tumors. Nucleosides such as 1-beta-D-arabinofuranosylcytosine (araC), 6-mercaptopurine, fludarabine and cladribine play an important role leukemias, while gemcitabine, 5-fluorouracil its prodrugs are extensively many types solid All these compounds metabolized similarly to endogenous nucleosides nucleotides. Active metabolites interfere with de novo synthesis nucleotides or inhibit DNA chain elongation after being incorporated into strand terminators. Furthermore, nucleoside antimetabolites induce strand-breaks finally cause apoptosis. target one more specific enzyme(s). The mode inhibitory action on enzyme is not always similar even among same base, araC gemcitabine. Although both phosphorylated by deoxycytidine kinase also good substrates cytidine deaminase, only gemcitabine shows antitumor against This suggests that differences pharmacological may reflect different modes molecules. design, vitro cytotoxicity, vivo activity, metabolism mechanism sugar-modified cytosine nucleosides, (2'S)-2'-deoxy-2'-C-methylcytidine (SMDC), 1-(2-deoxy-2-methylene-beta-D-erythro-pentofuranosyl)cytosine (DMDC), 1-(2-C-cyano-2-deoxy-1-beta-D-arabino-pentofuranosyl)cytosine (CNDAC) 1-(3-C-ethynyl-beta-D-ribo-pentofura-nosyl)cytosine (ECyd), developed our groups, discussed here.