西红花酸单糖糖苷合成及抗肿瘤活性研究Studiesonthesynthesis.PDF

西红花酸单糖糖苷合成及抗肿瘤活性研究 1 2 1 2 1* 李琪 ，谢水仙 ，邢菲菲 ，张俊国 ，张宏 （1.四川师范大学生命科学学院，四川 成都610101 ；2. 四川师范大学化学与材料科 学学院，四川 成都610068 ） 摘要：为探索西红花单糖糖苷的抗肿瘤活性，本文以E-1, 4-二-溴-2-丁烯、丙酮 醛缩二甲醇、E-2- 甲基-2-丁烯酸为初始原料合成西红花酸（7 ），最终合成西红花 1 13 单糖糖苷（9a~9f ），其结构经 H NMR 、 C NMR 及MS 确证。采用MTT 细胞 毒性实验对化合物 7、9a~9f 进行体外抗肿瘤活性筛选，通过流式细胞术检测抗 肿瘤活性高的目标产物对 HCT-116 细胞周期及细胞凋亡的影响。结果表明：化 合物7、9a、9e 和9f 对HCT-116 细胞及LOVO 细胞有明显的抑制作用，并且化 合物7、9e 和9f 可诱导HCT-116 肿瘤细胞凋亡、阻止细胞周期进程。合成的 红花糖苷抗结肠癌细胞活性趋势是五碳糖优于六碳糖。该合成方法简单且产率 高，对西红花糖苷的结构改造及其后续抗肿瘤活性研究具有一定的参考价值。 关键词：西红花单糖糖苷；合成方法；抗肿瘤活性；细胞凋亡 中图分类号：R916 文献标志码：A Studies on the synthesis and antitumor activities of crocins 1 2 1 2 1* LI Qi , XIE Shui-xian , XING Fei-fei , ZHANG Jun-guo , ZHANG Hong (1.College of Life Sciences, Sichuan Normal University, Chengdu 610101, China; College of Chemical and Material Science, Sichuan Normal University, Chengdu 610068, China) Abstract: To investigate the antitumor activities in vitro, the series of crocin derivatives (9a~9f) were designed and synthesized from crocetin, which was generated by starting reactants of E-1, 4-dibrom-2-butene, pyruvic aldehyde dimethyl acetal and trans-2, 3 -dimethylacrylic acid. The structures were confirmed by 1H 收稿日期：20 15-07-29 ；修回日期：20 15-11-02 基金项目：国家自然科学基金资助项目 （NO） *通讯作者Tel/Fax ：1800802 1106，E-mail: zhanghong651@ NMR, 13C NMR and mass spectrometry. Their in vitro cytotoxicities against various cancer cell lines (HCT-116, HT-29 and LOVO) were evaluated by MTT assay. The effects of the compounds on cell cycle and cell apoptosis of HCT-116 were detected by flow cytometry. The results showed that the compounds (7, 9a, 9e and 9f) had significant inhibitory effects on both HCT-116 and LOVO cells. T