Abstract
Even though sulfasalazine is drug of choice for treatment of ulcerative colitis (UC), 5-aminosalicylicacid (5-ASA)-induced pancreatitis and sulfapyridine-induced hepatitis are well documented in the literature. 4-aminosalicylic acid (4-ASA) is a promising but unexplored alternative, offering a lower risk of pancreatitis than 5-ASA. According to recent reports, a nutritional supplement of glucosamine could be useful in UC by suppressing activation of intestinal epithelial cells. Considering these findings, amide conjugates of aminosalicylates with D-glucosamine were synthesized by DCC coupling. In vitro release was studied in aqueous buffers, tissue homogenates of stomach/small intestine and rat cecal/fecal matter while therapeutic efficacy was evaluated in trinitrobenzenesulphonic acid (TNBS)-induced experimental colitis. The ameliorating effect of 5-ASA prodrug on the course of TNBS- induced colitis was comparable, while that for 4-ASA prodrug was moderate compared to sulfasalazine. Combination co-drug therapy of aminosalicylates with D-glucosamine offers an innovative and attractive platform that could be explored further for the safer management of UC.
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