Shuto S, Itoh H, Sakai A, Nakagami K, Imamura S, Matsuda A
Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Bioorg Med Chem. 1995 Mar;3(3):235-43. doi: 10.1016/0968-0896(95)00003-y.
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.
5'-磷脂酰-5-氟尿苷，其骨架结构与天然磷脂相同，其中常见磷脂的极性头部基团被5-氟尿苷取代，被设计为强效抗肿瘤剂。通过磷脂酶D催化相应的磷脂酰胆碱和5-氟尿苷的转磷脂酰化反应，合成了在甘油部分具有各种二酰基或二烷基残基的5'-磷脂酰-5-氟尿苷。通过腹腔注射和口服给药，在患有实验性肿瘤的小鼠中对这些新化合物进行了评估。二棕榈酰和二硬脂酰衍生物1b和1c对小鼠的P388白血病和Meth A纤维肉瘤均具有最大的抗肿瘤活性。
