Evaluation of the anti-inflammatory and analgesic activity of Me-UCH9, a dual cyclooxygenase-2/5-lipoxygenase inhibitor

Recently, we reported the dual inhibition of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LO) activity by some phenylsulphonyl urenyl chalcone derivatives. 2,4-dichloro-4'N[ N'(4"methylphenylsulphonyl)urenyl] chalcone (Me-UCH9), was selected in the present study to determine its potential anti-inflammatory and analgesic effect after oral administration in several animal models related to the activation of COX-2 and 5-LO pathways. In the zymosan stimulated mouse air pouch model, Me-UCH9, reduced in a dose-dependent manner leukotriene B-4 (LTB4) levels in pouch exudates obtained at 4 h, as well as prostaglandin E-2 (PGE(2)) generated through COX-2 activation at 24 It. Tumor necrosis factor alpha (TNF-alpha) and myeloperoxidase activity were also strongly inhibited in this model. Me-UCH9 significantly reduced gramilome size and vascular index determined in the murine air pouch granuloma model of angiogenesis. In the carrageenan-induced paw edema, this compound inhibited inflammatory response and pain, as well as PGE, and LTB4 content in paw edematous fluid. Analgesic properties were corroborated in the murine phenyl-p-benzoquinone-induced writhing test. Finally, Me-UCH9 exerted anti-inflammatory effects in the chronic model of rat adjuvant-induced arthritis, both inhibiting paw swelling and reducing PGE2 content. Our findings confirm that Me-UCH9 can modulate inflammatory and nociceptive responses in relation to the dual inhibition of COX-2 and 5-LO activities presented by this compound. (c) 2007 Elsevier Inc. All rights reserved.