新型齐墩果酸和熊果酸衍生物的合成、表征及细胞毒活性研究
收稿日期: 2018-05-15
修回日期: 2018-06-15
网络出版日期: 2018-08-23
基金资助
国家自然科学基金（No.21101067）资助项目.
Synthesis, Characterization and Cytotoxic Activity of Novel Oleanolic Acid and Ursolic Acid Derivatives
Received date: 2018-05-15
Revised date: 2018-06-15
Online published: 2018-08-23
Supported by
Project supported by the National Natural Science Foundation of China (No. 21101067).
以齐墩果酸和熊果酸为先导化合物，在C-28位分别导入戊二酸和乙醇酸连接片段，然后与吗啉、N-甲基哌嗪及N-Boc乙二胺进行偶联，得到20种新型齐墩果酸和熊果酸衍生物.采用3-（4，5-二甲基-2-噻唑）-2，5-二苯基溴化四氮唑噻唑蓝（MTT）法观察其对人肺腺癌细胞A549、人乳腺癌细胞MCF-7和人肝肿瘤细胞HepG2的抑制作用，结果表明齐墩果烷-2，12-二烯-28-酸-[1-（2-氨基-乙氨基）-1-氧亚基]乙酯（OA-9d）和熊果烷-2，12-二烯-28-酸-[1-（2-氨基-乙氨基）-1-氧亚基]乙酯（UA-9d）对三种人类癌症细胞株的活性明显优于先导化合物；并采用缺氧反应原件（HRE）依赖性分子测定法测定UA-9d抑制肝癌细胞Hep3B缺氧诱导因子1α（HIF-1α）表达的能力，实验结果表明，UA-9d能够有效地抑制HIF-1α的表达.
刘新宇 , 高雪琴 , 金学军 , 赵春晖 , 冯中华 , 隋悦 , 赵龙铉 , 阎欣 . 新型齐墩果酸和熊果酸衍生物的合成、表征及细胞毒活性研究[J]. 有机化学, 2018 , 38(12) : 3227 -3235 . DOI: 10.6023/cjoc201805030
Twenty oleanolic acid and ursolic acid derivatives were prepared by a modification at C-28 position via introduction with 1,5-pentanedioic acid and glycolic acid followed by amidation with amines, such as morpholine, N-methyl piperazine and N-Boc-ethylenediamine. Their in vitro anticancer activities towards A549, MCF-7 and HepG2 cell lines were evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide (MTT) method. The results indicated that the anticancer activities of olean-2,12-diene-28-oic acid[1-(2-amino-ethylamino)-1-oxo]ethyl ester (OA-9d), urs-2,12-diene-28-oic acid[1-(2-amino-ethylamino)-1-oxo]ethyl ester (UA-9d) against A549, MCF-7 and HepG2 cells are obviously better than those of lead compounds. The ability of UA-9d to inhibit the expression of hypoxia inducible factor-1α (HIF-1α) in hepatocellular carcinoma Hep3B cells was determined by hypoxia response element (HRE)-dependent molecular assay. The results showed that UA-9d could effectively inhibit the expression of HIF-1α.
Key words： oleanolic acid; ursolic acid; cytotoxic activity
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