新型CDDO衍生物的合成及抗肿瘤活性

Synthesis and antitumor activity of novel CDDO derivatives

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。

Abstract: 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.