title: Evaluation of the anti-inflammatory and analgesic activity of Me-UCH9, a dual cyclooxygenase-2/5-lipoxygenase inhibitor.
abstract: 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) (LTB(4)) levels in pouch exudates obtained at 4 h, as well as prostaglandin E(2) (PGE(2)) generated through COX-2 activation at 24 h. Tumor necrosis factor alpha (TNF-alpha) and myeloperoxidase activity were also strongly inhibited in this model. Me-UCH9 significantly reduced granuloma 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(2) and LTB(4) 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 PGE(2) 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.
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, University of Valencia, Av. Vicent Andrés Estellés s/n, 46100 Burjassot, Valencia, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Araico
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, University of Valencia, Av. Vicent Andrés Estellés s/n, 46100 Burjassot, Valencia, Spain.
authors.forename: M C
authors.initials: MC
authors.lastname: Terencio
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, University of Valencia, Av. Vicent Andrés Estellés s/n, 46100 Burjassot, Valencia, Spain.
authors.forename: M J
authors.initials: MJ
authors.lastname: Alcaraz
authors.affiliation: Laboratory of Organic Synthesis, Faculty of Pharmacy, Central University of Venezuela, Caracas 1051, Venezuela.
authors.forename: J N
authors.initials: JN
authors.lastname: Domínguez
authors.affiliation: Laboratory of Organic Synthesis, Faculty of Pharmacy, Central University of Venezuela, Caracas 1051, Venezuela.
authors.forename: C
authors.initials: C
authors.lastname: León
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, University of Valencia, Av. Vicent Andrés Estellés s/n, 46100 Burjassot, Valencia, Spain. Electronic address: Luisa.ferrandiz@uv.es.
authors.forename: M L
authors.initials: ML
authors.lastname: Ferrándiz
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001169:Arthritis, Experimental; D002351:Carrageenan / Q000737:chemistry; D047188:Chalcones / Q000737:chemistry / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000737:chemistry*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000188:drug therapy; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D016859:Lipoxygenase Inhibitors; D051379:Mice; D051381:Rats; D017208:Rats, Wistar
chemical_list: C521001:2,4-dichloro-4'N(N'(4''methylphenylsulfonyl)urenyl)chalcone; D000700:Analgesics; D000893:Anti-Inflammatory Agents; D047188:Chalcones; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D016859:Lipoxygenase Inhibitors; D002351:Carrageenan; D051546:Cyclooxygenase 2