目的 设计合成 5-氟尿嘧啶半乳糖衍生物,并对其抗肿瘤活性进行评价.方法 以5-氟尿嘧啶结构为基础,化学合成 3-全乙酰化半乳吡喃糖基-5-氟尿嘧啶(3-PGF),采用质谱(MS)及核磁共振氢谱(1H-NMR)对其结构进行表征;MTT比色分析法比较 3-PGF与 5-FU作用于人结肠癌细胞(SW-1116)及正常人肠上皮细胞(HIEC)后,其对细胞生长抑制率的差异.结果 MS和1H-NMR的结果确证合成化合物为目标产物;体外实验结果表明,3-PGF(0.01～100 μmol·L-1)作用于 SW-1116细胞 48 h后,其对细胞的生长抑制率为 8.45%～65.53%,呈浓度依赖性.在 HIEC细胞中,3-PGF的细胞生长抑制作用明显低于 5-FU.结论 本实验成功合成了 5-氟尿嘧啶半乳糖衍生物--3-全乙酰化半乳吡喃糖基-5-氟尿嘧啶,不仅具有较好的抗肿瘤活性,同时,该衍生物的毒性明显低于 5-FU,为 5-FU衍生物的设计合成提供了新的思路.%Aim To design and prepare a 5-fluoroura-cil-galactoside derivative and determine its antitumor activity in vitro. Methods Based on the molecular structure of 5-fluorouracil, 3-peracetylated galactopyr-anosyl-5-fluorouracil ( 3-PGF ) was synthesized and I-dentified using MS and 1 H-NMR. After treatments with 5-FU and 3-PGF, the growth inhibitory rates on human colon cancer cells ( SW-1116 ) and human intestinal epithelial cells ( HIEC ) were detected using MTT assay. Results The 5-fluorouracil-galactoside derivative was prepared and the structure of it was determined by MS and :H-NMR as 3-peracetylated galactopyranosyl-5-fluorouracil. And the growth inhibitory rates of 3-PGF ( 0. 01 ~ 100 umol . L-1 ) on SW-1116 cells for 48 h were 28. 45% ~ 64. 04%. At the same time, 3-PGF had lower inhibitory rates on HIEC than 5-FU. Conclusions The 5-fluorouracil-galactoside derivative, 3-peracetylated galactopyranosyl-5-fluorouracil, which was synthesized successfully in our lab , has a good antitumor activity. Furthermore, it is less toxic than 5-fluorouracil and gives some novel thoughts for design and synthesis of 5-fluorouracil derivatives.
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