本文選題：齊墩果酸類似物　切入點：合成　出處：《有機化學》2017年06期 　論文類型：期刊論文

【摘要】：以天然產(chǎn)物齊墩果酸為母體,采用計算機藥物輔助設(shè)計,在C-kit與活性小分子進行模擬對接的基礎(chǔ)上,在A環(huán)上引入含氮、氧雜環(huán),同時對其C(28)位羧基進行酰胺化結(jié)構(gòu)修飾,設(shè)計并合成了10個新的齊墩果酸類似物,其結(jié)構(gòu)經(jīng)過~1HNMR、~(13)CNMR、MS等確認.采用噻唑藍(MTT)法,選用人口腔表皮樣癌細胞(KB)和人肺癌細胞(A549)進行了初步的體外抗腫瘤活性篩選.結(jié)果表明,測試的化合物對兩種細胞均具有一定的抑制活性,其中齊墩果-2,12-二烯并[3,2-d]嘧啶-28-羧酸正己酯(I_4)和5',6'-二氫-齊墩果-2-烯并[2,3-b]吡嗪-12-烯-28-酰-4''-甲基苯胺(Ⅱ_3)對A549腫瘤細胞表現(xiàn)出很強的抑制活性,在10μg/mL濃度下IC_(50)值分別為2.67和1.03μmol/L,活性明顯高于5-氟尿嘧啶(IC_(50)=7.39μmol/L),值得進一步研究.
[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，

本文編號：1609770