Biological evaluation of 2-(4-amino-phenyl)-3-(3,5-dihydroxylphenyl) propenoic acid

Basic Clin Pharmacol Toxicol. 2009 Nov;105(5):350-6. doi: 10.1111/j.1742-7843.2009.00463.x. Epub 2009 Sep 8.

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 IC(50) = 2.20 microM, COX-2 IC(50) = 1.76 microM) and 5-LOX (IC(50) = 0.28 microM) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aniline Compounds / adverse effects
  • Aniline Compounds / pharmacology*
  • Aniline Compounds / therapeutic use
  • Animals
  • Anti-Inflammatory Agents / adverse effects
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents / therapeutic use
  • Caffeic Acids / adverse effects
  • Caffeic Acids / pharmacology*
  • Caffeic Acids / therapeutic use
  • Carrageenan
  • Cyclooxygenase Inhibitors / adverse effects
  • Cyclooxygenase Inhibitors / pharmacology*
  • Cyclooxygenase Inhibitors / therapeutic use
  • Edema / chemically induced
  • Edema / drug therapy
  • Edema / metabolism
  • Lipoxygenase Inhibitors*
  • Male
  • Mice
  • Mice, Inbred ICR
  • Rats
  • Rats, Sprague-Dawley
  • Stomach Ulcer / chemically induced

Substances

  • 2-(4-aminophenyl)-3-(3,5-dihydroxylphenyl)propenoic acid
  • Aniline Compounds
  • Anti-Inflammatory Agents
  • Caffeic Acids
  • Cyclooxygenase Inhibitors
  • Lipoxygenase Inhibitors
  • Carrageenan