Biological evaluation of 2-(4-Amino-Phenyl)-3-(3,5-Dihydroxylphenyl) propenoic acid

Abstract

2-(4-Aminophenyl)-3-(3,5-dihydroxylphenyl) propenoic acid (CSN-07001) is a new compound based on the combination of resveratrol and propenoic acid derivatives. In vitro cyclooxygenase (COX)/5-lipoxygenase (5-LOX) inhibition assays showed that the test compound exhibited a dual inhibitory activity against the COX (COX-1 IC50 = 2.20 μM, COX-2 IC50 = 1.76 μM) and 5-LOX (IC50 = 0.28 μM) enzymes. Further, the enhanced COX-1/COX-2/5-LOX expression in lipopolysaccaride-induced lung inflammation in mice was also suppressed by CSN-07001 in a concentration- dependent manner. In vivo studies showed that CSN-07001 exhibited potent anti-inflammatory and antinociceptive effects in different experimental models. We further examined the risk of gastric damage induced by CSN-07001. The test compound was gastric-sparing in that it elicited markedly fewer stomach lesions than indomethacin in rats. Taken together, our data indicate that CSN-07001 exhibits a novel class of dual inhibitors of COX and 5-LOX having therapeutic potential as non-steroidal anti-inflammatory agents with an enhanced gastric safety profile. © 2009 Nordic Pharmacological Society.