摘要
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。
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 ^1 HNMR, 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） ,SKHEP-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.
出处
《第二军医大学学报》
CAS
CSCD
北大核心
2008年第12期1470-1474,共5页
Academic Journal of Second Military Medical University
关键词
去甲斑蝥素
合成
抗肿瘤药
norcantharidin
synthesis
antineoplastic agents
