CC 05, a novel anti-inflammatory compound, exerts its effect by inhibition of cyclooxygenase-2 activity.
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 (CC 05) in vitro and in vivo. In an in vitro cell-based assay, CC 05 inhibited cyclooxygenase (COX)-2-derived prostaglandin E(2) (PGE(2)) synthesis with an IC(50) value of 0.328+/-0.04 microM compared with an IC(50) value of 14.34+/-0.05 microM for the inhibition of COX-1-derived PGE(2) synthesis. In two in vivo rodent models, CC 05 (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 PGE(2) production in the inflamed pouch dose-dependently without affecting the PGE(2) production in stomachs. Furthermore, CC 05 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 CC 05 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.
Yin
Lin-Lin
LL
Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, China.
Zhang
Wei-Yu
WY
Li
Ming-Hui
MH
Shen
Jing-Kang
JK
Zhu
Xing-Zu
XZ
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D016367:Baculoviridae / Q000235:genetics*; D002351:Carrageenan; D000068579:Celecoxib; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D007213:Indomethacin / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced / Q000517:prevention & control; D020128:Inhibitory Concentration 50; D008297:Male; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018411:Spodoptera / Q000187:drug effects / Q000378:metabolism / Q000821:virology*; D013449:Sulfonamides / Q000494:pharmacology*; D000096926:Benzenesulfonamides
D000893:Anti-Inflammatory Agents; D002351:Carrageenan; D000068579:Celecoxib; D016861:Cyclooxygenase Inhibitors; D015232:Dinoprostone; D007213:Indomethacin; D011720:Pyrazoles; D013449:Sulfonamides; D000096926:Benzenesulfonamides