新型CDDO衍生物的合成及抗肿瘤活性  

Synthesis and antitumor activity of novel CDDO derivatives

作　　者：裴江鸿 肖余 李其星[1] 赵子豪 陈莉[1] 

机构地区：[1]中国药科大学天然药物化学教研室,南京210009

出　　处：《中国药科大学学报》2017年第5期548-553,共6页Journal of China Pharmaceutical University

摘　　要：对2-氰基-3,12-二氧代齐墩果烷-1,9(11)-二烯-28-羧酸(CDDO)进行结构修饰,通过不同连接臂将几种含氮杂环分别引入C-17位羧基,设计并合成了12个未见文献报道的新化合物(9a^9l),其结构经ESI-MS、IR和~1H NMR确认。采用MTT法评价了化合物对HCT-116、A549及HepG2肿瘤细胞的抑制活性。实验结果表明,部分化合物对肿瘤细胞具有较强的抑制活性,其中化合物9c的活性最强,高于CDDO咪唑啉酮衍生物(CDDO-Im)。血浆稳定性实验表明,化合物9c的血浆稳定性较高,显著高于CDDO-Im。Twelve novel 2-cyano-3,12-dioxooleana-1,9（11）-dien-28-oic acid（CDDO）derivatives were designed and synthesized（9a-9l）by introducing different heterocyclic rings to 17-COOH of CDDO through various linkers.Their structures were determined by ESI-MS,IR and ~1H NMR.The antiproliferative activity of the synthetic derivatives against human cancer cells HCT-116,A549 and HepG2 was evaluated by MTT assay.Several compounds showed potent inhibitory activities against test cell lines.Among them,compound 9c showed more potent antiproliferative activity than the CDDO-imidazolide（CDDO-Im）.Moreover,rat plasma stability assay showed that compound 9c was more stable than CDDO-Im.

关 键 词：2-氰基-3 12-二氧代齐墩果烷-1 9(11)-二烯-28-羧酸 衍生物 合成 抗增殖活性 血浆稳定性 

分 类 号：R914[医药卫生—药物化学]