Identification of a new azoreductase driven prodrug from bardoxolone methyl and 5-aminosalicylate for the treatment of colitis in mice.
10.1016/S1875-5364(21)60055-9
- Author:
Xin QIAO
1
,
2
;
Yan GONG
3
;
Yi MOU
4
;
Yi-Hua ZHANG
1
,
5
;
Zhang-Jian HUANG
1
,
6
;
Xiao-Dong WEN
1
,
7
Author Information
1. State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China
2. School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
3. Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University, Nanjing 210009, China.
4. College of Pharmacy and Chemistry & Chemical Engineering, Taizhou University, Taizhou 225300, China.
5. Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University, Nanjing 210009, China.
6. Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University, Nanjing 210009, China. Electronic address: cpudahuang@163.com.
7. School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 210009, China. Electronic address: xiaodongwen@cpu.edu.cn.
- Publication Type:Journal Article
- Keywords:
5-Aminosalicylate;
Azoreductase;
Bardoxolone Methyl;
Prodrug;
Ulcerative colitis
- MeSH:
Animals;
Colitis/drug therapy*;
Mesalamine/pharmacology*;
Mice;
Nitroreductases;
Oleanolic Acid/pharmacology*;
Prodrugs
- From:
Chinese Journal of Natural Medicines (English Ed.)
2021;19(7):545-550
- CountryChina
- Language:English
-
Abstract:
For local treatment of ulcerative colitis, a new azoreductase driven prodrug CDDO-AZO from bardoxolone methyl (CDDO-Me) and 5-aminosalicylate (5-ASA) was designed, synthesized and biologically evaluated. It is proposed that orally administrated CDDO-AZO is stable before reaching the colon, while it can also be triggered by the presence of azoreductase in the colon to fragment into CDDO-Me and 5-ASA, generating potent anti-colitis effects. Superior to olsalazine (OLS, a clinically used drug for ulcerative colitis) and CDDO-Me plus 5-ASA, CDDO-AZO significantly attenuated inflammatory colitis symptoms in DSS-induced chronic colitis mice, which suggested that CDDO-AZO may be a promising anti-ulcerative colitis agent.
