Nucleosides and nucleotides. 155. Synthesis, antitumor effects, and possible enzymatic activation mechanism of 5'-phosphatidyl-2'-deoxy-2'-methylenecytidine (DMDC)

Article abstract of DOI:10.1016/0960-894X(96)00389-7

2'-Deoxy-2'-methylenecytidine (DMDC, 1) and its 5-fluoro congener (5-F-DMDC, 2), potent antitumor nucleosides developed by us, were efficiently converted to their 5'-phosphatidyl derivatives bearing palmitoyl residues (3 and 4, respectively) as novel antitumor phospholipids by phospholipase D-catalyzed trans-phosphatidylation. These phospholipids 3 and 4, administered i.p., remarkably prolonged the life-span of mice which were i.p.-inoculated with M5076 sarcoma, and the effects were clearly superior to that of DMDC. Compound 3 was a good substrate for phospholipase A₂ from bovine pancreas as well as phospholipase D from Streptomyces, while it was slightly hydrolyzed by phospholipase C from Bacillus cereus.