CC05, a novel anti-inflammatory compound, exerts its effect by inhibition of cyclooxygenase-2 activity

Abstract

In the present study, we examined the anti-inflammation of a novel compound, 4-[5-(3-amino-4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide (CC05) in vitro and in vivo. In an in vitro cell-based assay, CC05 inhibited cyclooxygenase (COX)-2-derived prostaglandin E2 (PGE2) synthesis with an IC50 value of 0.328±0.04 μM compared with an IC50 value of 14.34±0.05 μM for the inhibition of COX-1-derived PGE2 synthesis. In two in vivo rodent models, CC05 (12.5, 25 and 50 mg/kg, i.g.) is a moderate potential and selective inhibitor of COX-2. It can reduce carrageenan-induced paw edema and PGE2 production in the inflamed pouch dose-dependently without affecting the PGE2 production in stomachs. Furthermore, CC05 had no effect on COX-2 mRNA and protein expression in phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 human macrophages stimulated with lipopolysaccharide (LPS). These results demonstrate that CC05 is a novel COX-2 inhibitor and the anti-inflammatory action is not directed towards the transcription or translation of the COX-2 gene but only to the enzymatic activity of the protein.