Sulfonamide derivatives of styrylheterocycles as a potent inhibitor of COX-2-mediated prostaglandin E2 production

The overproduction of prostaglandin E-2 (PGE(2)) plays an important role in a variety of pathophysiological processes including inflammation and carcinogenesis. Therefore, the modulation of PGE(2) production is a promising target in the design of chemotherapeutic agents. In the present study, the inhibitory effects of a series of styrylheterocycles having either a p-SO2NH2 or p-SO2Me group on the production of cyclooxygenase-2-mediated PGE(2) were evaluated in lipopolysaccharide-stimulated RAW264.7 murine macrophages. Among the series of styrylheterocycle derivatives, (E)-4-(2-(thiophen-3-yl)vinyl) benzenesulfonamide exhibited a potent inhibitory activity, with an IC50 value of 0.013 mu M. The inhibitory activity against the overproduction of PGE(2) by the active compound was found to be due in part to the suppression of COX-2 mRNA expression. (C) 2010 Elsevier Ltd. All rights reserved.