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: A Araico, M C Terencio, M J Alcaraz, J N Domínguez, C León, M L Ferrándiz
• Journal: Life sciences (Life Sci) Vol. 80 Issue 23 Pg. 2108-2117 (May 16 2007) ISSN: 0024-3205 [Print] Netherlands
• PMID: 17490689 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 2,4-dichloro-4'N(N'(4''methylphenylsulfonyl)urenyl)chalcone
• Analgesics
• Anti-Inflammatory Agents
• Chalcones
• Cyclooxygenase Inhibitors
• Enzyme Inhibitors
• Lipoxygenase Inhibitors
• Carrageenan
• Cyclooxygenase 2

Topics

• Analgesics (pharmacology)
• Animals
• Anti-Inflammatory Agents (pharmacology)
• Arthritis, Experimental
• Carrageenan (chemistry)
• Chalcones (chemistry, pharmacology)
• Cyclooxygenase 2 (chemistry)
• Cyclooxygenase Inhibitors (pharmacology)
• Dose-Response Relationship, Drug
• Edema (drug therapy)
• Enzyme Inhibitors (pharmacology)
• Female
• Humans
• Lipoxygenase Inhibitors
• Mice
• Rats
• Rats, Wistar