Identification of a new azoreductase driven prodrug from bardoxolone methyl and 5-aminosalicylate for the treatment of colitis in mice

摘要

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.