Synthesis and antitumor activities of novel CDDO-Me analogues
10.11665/j.issn.1000-5048.20150305
- VernacularTitle:新型CDDO-Me类似物的合成及抗肿瘤活性
- Author:
Yixue QIAO
1
;
Yi MOU
;
Zhangjian HUANG
;
Yong AI
;
Fenghua KANG
;
Yisheng LAI
;
Yihua ZHANG
Author Information
1. 中国药科大学新药研究中心，天然药物活性组分与药效国家重点实验室，江苏省代谢性疾病药物重点实验室
- Publication Type:Journal Article
- Keywords:
oleanolic acid;
CDDO-Me;
synthesis;
antitumor activity
- From:
Journal of China Pharmaceutical University
2015;46(3):289-293
- CountryChina
- Language:Chinese
-
Abstract:
The novel oleanolic acid derivatives 2a-2e were synthesized by introducing an α, β-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, respectively. Derivatives 3a-3e were synthesized by substituting C-1 of compounds 2a-2e with bromine. The target compounds 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 μmol/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 addition, 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.
