State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University, Nanjing 210009, China.
Chin J Nat Med. 2021 Jul;19(7):545-550. doi: 10.1016/S1875-5364(21)60055-9.
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.
为了局部治疗溃疡性结肠炎，设计、合成并生物评估了一种新的偶氮还原酶驱动的前药 CDDO-AZO，它由 bardoxolone 甲基（CDDO-Me）和 5-氨基水杨酸（5-ASA）组成。据推测，口服给予的 CDDO-AZO 在到达结肠之前是稳定的，而在结肠中存在偶氮还原酶的情况下，它也可以被触发，从而断裂成 CDDO-Me 和 5-ASA，产生有效的抗结肠炎作用。与柳氮磺胺吡啶（OLS，一种用于溃疡性结肠炎的临床药物）和 CDDO-Me 加 5-ASA 相比，CDDO-AZO 显著减轻了 DSS 诱导的慢性结肠炎小鼠的炎症性结肠炎症状，这表明 CDDO-AZO 可能是一种有前途的抗溃疡性结肠炎药物。
