齐墩果酸A环衍生的类似物的合成及抗肿瘤活性研究

发布时间：2018-03-14 05:19

  本文选题：齐墩果酸类似物　切入点：合成　出处：《有机化学》2017年06期 　论文类型：期刊论文

【摘要】：以天然产物齐墩果酸为母体,采用计算机药物辅助设计,在C-kit与活性小分子进行模拟对接的基础上,在A环上引入含氮、氧杂环,同时对其C(28)位羧基进行酰胺化结构修饰,设计并合成了10个新的齐墩果酸类似物,其结构经过~1HNMR、~(13)CNMR、MS等确认.采用噻唑蓝(MTT)法,选用人口腔表皮样癌细胞(KB)和人肺癌细胞(A549)进行了初步的体外抗肿瘤活性筛选.结果表明,测试的化合物对两种细胞均具有一定的抑制活性,其中齐墩果-2,12-二烯并[3,2-d]嘧啶-28-羧酸正己酯(I_4)和5',6'-二氢-齐墩果-2-烯并[2,3-b]吡嗪-12-烯-28-酰-4''-甲基苯胺(Ⅱ_3)对A549肿瘤细胞表现出很强的抑制活性,在10μg/mL浓度下IC_(50)值分别为2.67和1.03μmol/L,活性明显高于5-氟尿嘧啶(IC_(50)=7.39μmol/L),值得进一步研究.
[Abstract]:The natural product oleanolic acid was used as the parent. On the basis of simulating the docking between C-kit and active small molecules, nitrogen and oxygen heterocycles were introduced into the A ring, and the carboxyl group at C _ (28) position was modified by amidation structure. Ten new oleanolic acid analogues were designed and synthesized, and their structures were confirmed by 1H NMR13 CNMRMS et al. The antitumor activity of KB (human oral epidermoid carcinoma cell) and A549 (human lung cancer cell line) were screened by thiazolyl blue MTT in vitro. The compounds tested have a certain inhibitory activity on both kinds of cells. Oleanolic fruit (Oleanolic fruit -2ON-12- dieno [3- 2-d] pyrimidine-28-hexyl n-hexyl) and Oleanose-dihydro-oleanolic-2-enzoate [23-b] pyrazine-12-ene-28acyl-4- (methylaniline) (鈪，

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