新型天麻素衍生物的设计、合成及抗肿瘤活性研究

摘要

以顺丁烯二酸酐为原料,依次经加成和取代反应制得一系列斑蝥素衍生物(3a~3c);以葡萄糖为原料,经乙酰化、溴化和甲基化反应制得乙酰天麻素(7);7与3a~3c经酯化反应合成了一系列新型天麻素衍生物(8a~8c);以5-氟尿嘧啶为原料,合成了新型天麻素衍生物(11),其结构经1H NMR, 13C NMR, IR和MS(ESI)表征.采用细胞增殖抑制实验法(MTT法)研究了8a~8c和11对肝癌细胞(HepG2和SMCC7721)的抑制活性.结果表明:8a,8b,8c和11对肝癌细胞株均有一定的抑制作用,其中8a的抑制活性最好,其IC50为55.33 μmol· L-1 (HepG2)和42.07 μmol· L-1(SMCC7721).%A series of cantharidin derivatives(3a~3c)were prepared from maleic anhydride via addi-tion reaction and substitution reaction.Acetagastrodin(7)was achieved from glucose via the reaction of acetylation,bromination and methylation.Three novel gastrodin derivatives(8a~8c)were synthesized by esterification of 3a~3c with 7.In addition,a novel gastrodin derivative(11)was synthesized from 5-fluorouracil.The structures were characterized by 1H NMR, 1 3C NMR,IR and MS(ESI).The anti-tumor activities of 8a ~8c and 11 against two human cancer cell lines, including HepG-2 and SMCC7721,were evaluated by MTT method.The results showed that,to some extent,8a~8c and 11 exhibited inhibitory effects on both hepatoma cell lines.Among them,8a demonstrated best cytotoxic activity against HepG-2 and SMCC7721, with IC50of 55.33 μmol· L-1and 42.07 μmol· L-1, re-spectively.