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 ...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.展开更多
基金supported by the National Natural Science Foundation of China(Nos.81773573 and 21977116)the Natural Science Fund for Colleges and Universities in Jiangsu Province(No.17KJB350011)+1 种基金the Open Project of State Key Laboratory of Natural Medicines(No.SKLNMZZCX201824)the State Key Laboratory of Pathogenesis,Prevention and Treatment of High Incidence Diseases in Central Asia(No.SKL-HIDCA-2018-1).
文摘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.
