中文摘要：

以齐墩果酸（OA）为起始原料,经9步反应合成了C环含有α,β-不饱和酮结构的2-氰基-3,12-二氧代齐墩果烷-1,9（11）-二烯-28-酸甲酯（CDDO-Me）活性类似物1,再将不同的脂肪羧酸和芳杂环羧酸分别与其C-3位羟基酯化,设计、合成了新型CDDO-Me类似物（2a~2e）,并进一步将C-1位溴代,得到化合物3a~3e。采用MTT法测定了目标化合物对肺癌细胞A549、肝癌细胞Hep G2以及肺上皮细胞BEAS-2B的增殖抑制活性。结果表明,目标化合物对Hep G2细胞和A549细胞的增殖均显示了不同程度的抑制,其中化合物3b和3c的抑制活性最强[IC50=（6.13±1.16）μmol/L,IC50=（5.49±1.03）μmol/L],优于先导物1,与CDDO-Me相当。此外,目标化合物对正常细胞BEAS-2B的抑制活性显著小于对上述两种肿瘤细胞的抑制活性,显示了较高的肿瘤细胞选择性,其中3e对Hep G2的选择性最高,其抑制作用是正常细胞的10倍,值得进一步研究。

英文摘要：

The novel oleanolic acid derivatives 2a-2e were synthesized by introducing an a, r-unsaturated ketone moiety to C-ring of oleanolic acid （OA） via a nine-step reaction sequence, yielding an active CDDO-Me analogue （1）, followed by coupling of C3-OH of 1 with various aliphatic and aromatic carboxylic acids, respective- ly. Derivatives 3a-3e were synthesized by substituting C-1 of compounds 2a-2e with bromine. The target com- pounds were characterized by IR, MS and 1H NMR spectra. All the target compounds showed strong inhibitory effects against two tumor cell lines （ HepG2 and A549） to a varying extent. The anti-proliferative activities of active compounds 3b and 3c （IC50 =6. 13 ± 1.16 μ mol/L and IC50 =5.49 ± 1.03 μmol/L, respectively） against HepG2 and A549 were more potent than compound 1 and comparable to the positive control CDDO-Me. In addi- tion, all the target compounds displayed much weaker anti-proliferative activity against the two tumor cell lines than that against normal BEAS-2B cells. Compound 3c showed ten-fold selective inhibition against HepG2 relative to BEAS-2B cells, and is thus worthy of further study.