NUCLEOSIDES AND NUCLEOTIDES .155. SYNTHESIS, ANTITUMOR EFFECTS, AND POSSIBLE ENZYMATIC ACTIVATION MECHANISM OF 5'-PHOSPHATIDYL-2'-DEOXY-2'-METHYLENECYTIDINE (DMDC)

Authors
SHUTO S AWANO H FUJII A YAMAGAMI K MATSUDA A
Citation
S. Shuto et al., NUCLEOSIDES AND NUCLEOTIDES .155. SYNTHESIS, ANTITUMOR EFFECTS, AND POSSIBLE ENZYMATIC ACTIVATION MECHANISM OF 5'-PHOSPHATIDYL-2'-DEOXY-2'-METHYLENECYTIDINE (DMDC), Bioorganic & medicinal chemistry letters, 6(18), 1996, pp. 2177-2182
Citations number
20
Categorie Soggetti
Chemistry Inorganic & Nuclear","Chemistry Medicinal
Journal title
Bioorganic & medicinal chemistry letters → ACNP
ISSN journal
0960894X
Volume
6
Issue
18
Year of publication
1996
Pages
2177 - 2182
Database
ISI
SICI code
0960-894X(1996)6:18<2177:NAN.SA>2.0.ZU;2-S
Abstract
2'-Deoxy-2'-methylenecytidine (DMDC, 1) and its 5-fluoro congener (5-F -DMDC, 2), potent antitumor nucleosides developed by us, were efficien tly converted to their 5'-phosphatidyl derivatives bearing palmitoyl r esidues (3 and 4, respectively) as novel antitumor phospholipids by ph ospholipase 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 cl early superior to that of DMDC. Compound 3 was a good substrate for ph ospholipase A(2) from bovine pancreas as well as phospholipase D from Streptomyces, while it was slightly hydrolyzed by phospholipase C from Bacillus cereus. Copyright (C) 1996 Elsevier Science Ltd