Design, synthesis and anti-inflammatory evaluation of CDDO-Me ester prodrugs
10.11665/j.issn.1000-5048.20160605
- VernacularTitle:CDDO-Me羧酸酯前药的设计、合成及抗炎活性
- Author:
Yi MOU
1
;
Tong CHEN
;
Zhangjian HUANG
;
Yisheng LAI
;
Sixun PENG
;
Hui JI
;
Yihua ZHANG
Author Information
1. 中国药科大学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；泰州学院医药与化学化工学院
- Publication Type:Journal Article
- Keywords:
oleanolic acid;
CDDO-Me prodrug;
anti-inflammatory activity;
synthesis
- From:
Journal of China Pharmaceutical University
2016;47(6):661-665
- CountryChina
- Language:Chinese
-
Abstract:
In order to search for new anti-inflammatory agents with strong activity and less toxicity relative to CDDO-Me, the ester prodrugs 2-8 of CDDO-Me were synthesized by treatment of oleanolic acid(OA)with DMF/K2CO3 to generate 1, followed by esterification of 1 with various aliphatic and aromatic carboxylic acids, respectively. All the target compounds showed strong inhibitory effects on LPS-induced NO production in RAW 264. 7 cells. Among them, compounds 2 and 7 possessed the most potent inhibitory effects with IC50=(2. 34±0. 67)and(3. 83±0. 97)nmol/L, respectively. Moreover, MTT assay indicated that all the target compounds(2-8)displayed much weaker anti-proliferative activity against RAW 264. 7 cell lines than CDDO-Me, suggesting that they may be less toxic than CDDO-Me.
