摘要/Abstract
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.
关键词: 齐墩果酸, 熊果酸, 细胞毒活性
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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