新型CDDO衍生物的合成及抗肿瘤活性

裴江鸿; 肖余; 李其星; 赵子豪; 陈莉

doi:10.11665/j.issn.1000-5048.20170507

新型CDDO衍生物的合成及抗肿瘤活性

中国药科大学天然药物化学教研室

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- 刊出日期: 2017-10-24

Synthesis and antitumor activity of novel CDDO derivatives

摘要

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。
- 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
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.
- CDDO /
- derivative /
- synthesis /
- antiproliferative activity /
- plasma stability

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参考文献(12)

[1]	Pollier J,Goossens A.Oleanolic acid[J].Phytochemistry,2012,77(5):10-15.
[2]	Sporn MB,Liby KT,Yore MM,et al.New synthetic triterpenoids:potent agents for prevention and treatment of tissue injury caused by inflammatory and oxidative stress[J].J Nat Prod,2011,74(3):537-545.
[3]	Liby KT,Sporn MB.Synthetic oleanane triterpenoids:multifunctional drugs with a broad range of applications for prevention and treatment of chronic disease[J].Pharmacol Rev,2012,64(4):972-1003.
[4]	Liby KT, Yore MM, Sporn MB. Triterpenoids and rexinoids as multifunctional agents for the prevention and treatment of cancer[J].Nat Rev Cancer,2007,7(5):357-369.
[5]	Liby K,Yore MM,Roebuck BD,et al.A novel acetylenic tricyclic bis-(cyano enone)potently induces phase 2 cytoprotective pathways and blocks liver carcinogenesis induced by aflatoxin[J].Cancer Res,2008,68(16):6727-6733.
[6]	Hong DS,Kurzrock R,Supko JG,et al.A phase I first-in-human trial of bardoxolone methyl in patients with advanced solid tumors and lymphomas[J].Clin Cancer Res,2012,18(12):3396-3406.
[7]	Pergola PE,Raskin P,Toto RD,et al.Bardoxolone methyl and kidney function in CKD with type 2 diabetes[J].N Engl J Med,2011,365(4):327-336.
[8]	Chartoumpekis DV, Sykiotis GP. Bardoxolone methyl in type 2 diabetes and advanced chronic kidney disease[J].N Engl J Med,2014,370(18):1767-1769.
[9]	de Zeeuw D,Akizawa T,Audhya P,et al.Bardoxolone methyl in type 2 diabetes and stage 4 chronic kidney disease[J].N Engl J Med,2013,369(26):2492-2503.
[10]	Taylor RD,MacCoss M,Lawson ADG.Rings in drugs[J].J Med Chem,2014,57(14):5845-5859.
[11]	Xiao Y,Luo QF,Li QX,et al.Improved synthesis of 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid[J].Chin J Med Chem(中国药物化学杂志),2016,26(2):131-135.
[12]	Liu Y,Wang TT,Chen L.Synthesis and antitumor activity of isosteviol derivatives[J].J China Pharm Univ(中国药科大学学报),2016,47(1):48-53.

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新型CDDO衍生物的合成及抗肿瘤活性

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Synthesis and antitumor activity of novel CDDO derivatives

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