A double prodrug system for colon targeting of benzenesulfonamide COX-2 inhibitors
Item Type:Journal Article
Citation:Marquez Ruiz JF, Kedziora K, Keogh B, Maguire J, Reilly M, Windle HJ, Kelleher D, Gilmer JF, A double prodrug system for colon targeting of benzenesulfonamide COX-2 inhibitors, Bioorganic & Medicinal Chemistry Letters, 21, 22, 2011, 6636-6640
A double prodrug system for colon targeting of benzenesulfonamide COX-2 inhibitors.pdf (Published (author's copy) - Peer Reviewed) 303.3Kb
The design, synthesis and delivery potential of a new type of benzenesulfonamide cyclo-oxygenase-2 (COX-2) inhibitor prodrug is investigated using celecoxib. The approach involves a double prodrug that is activated first by azoreductases and then by cyclization triggering drug release. We studied the intramolecular aminolysis of the acylsulfonamide. The cyclization was surprisingly rapid at physiological pH and very fast at pH 5. The prodrug is activated specifically under conditions found in the colon but highly stable in the presence of human and rodent intestinal extracts. Finally, the prototype with celecoxib was transported much more slowly in the Caco-2 transepithelial model than the parent. The design therefore shows significant promise for the site specific delivery of benzenesulfonamide COX-2 inhibitors to the colon.
Type of material:Journal Article
Series/Report no:Bioorganic & Medicinal Chemistry Letters
Availability:Full text available