Nucleosides and nucleotides--CXXXVII. Antitumor phospholipids with 5-fluorouridine as a cytotoxic polar-head: synthesis of 5'-phosphatidyl-5-fluorouridines by phospholipase D-catalyzed transphosphatidylation.
5'-Phosphatidyl-5-fluorouridines, with the same backbone structure as that of natural phospholipids, in which a polar-head group of usual phospholipids is replaced by 5-fluorouridine, were designed to be potent antitumor agents. 5'-Phosphatidyl-5-fluorouridines with a variety of diacyl or dialkyl residues in the glycerol moiety, were synthesized by phospholipase D-catalyzed transphosphatidylation from the corresponding phosphatidylcholine and 5-fluorouridine. These new compounds were evaluated in mice with experimental tumors by ip and po administration. Dipalmitoyl and distearoyl derivatives 1b and 1c had the greatest antitumor activity against both P388 leukemia and Meth A fibrosarcoma in mice.
Shuto
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S
Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Itoh
H
H
Sakai
A
A
Nakagami
K
K
Imamura
S
S
Matsuda
A
A
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005354:Fibrosarcoma / Q000188:drug therapy; D007941:Leukemia P388 / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D009368:Neoplasm Transplantation; D010712:Phosphatidic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010739:Phospholipase D / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D014529:Uridine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000970:Antineoplastic Agents; D010712:Phosphatidic Acids; C001943:5-fluorouridine; D010739:Phospholipase D; D014529:Uridine