新型去甲斑蝥素衍生物的设计合成及体外抗肿瘤活性

目的:设计合成新型去甲斑蝥素衍生物，并研究其体外抗肿瘤活性。方法:以呋喃和马来酸酐为起始原料经多步反应合成去甲斑蝥素衍生物,化合物经1HNMR、ESI-MS和元素分析确证结构；用MTT法,首先对所有化合物进行抗乳腺癌细胞株4T1体外活性筛选,然后对活性较好的化合物7a和7c进一步作抗肺癌细胞株LLC和抗肝癌细胞株SK-HEP-1的活性检测,同时对这2种化合物进行对正常血管内皮细胞ABAE的损伤试验。结果:设计合成了18种新化合物。其中化合物7a 和7c对肿瘤细胞株有一定的抑制作用,而对正常细胞的损伤程度较低。结论:化合物7a 和7c对乳腺癌细胞株4T1、肺癌细胞株LLC和肝癌细胞株SK-HEP-1有一定的抑制作用,尤其是化合物7c对正常内皮细胞ABAE的损伤比对照药去甲斑蝥素小得多,有进一步研究的价值。

Design,synthesis and anti-tumor activity of novel norcantharidin derivatives

Objective:To design and synthesize novel norcantharidin derivatives and to investigate their anti-tumor activities in vitro.Methods: Novel norcantharidin analogues were synthesized through several steps using furan and maleic anhydride as the starting material.All the target compounds were confirmed by 1HNMR,ESI-MS and element analysis,and screened against 4T1(breast cancer cell).The compound 7a and 7c with better activity were further screened against LLC(lung cancer cell),SK-HEP-1(human hepatoma cell) and ABAE(vascular endothelial cell).Results: Totally 18 novel target compounds were obtained.The results of anti-cancer test showed that compounds 7a and 7c had anti-tumor activity and less damage to normal cells.Conclusion: Compounds 7a and 7c have inhibitory effect against 4T1 cells,LLC cells and SK-HEP-1 cells.Compound 7c shows less damage to ABAE(normal vascular endothelial cells) than norcantharidin and is worth further studying.