Biological evaluation of 2-(4-amino-phenyl)-3-(3,5-dihydroxylphenyl) propenoic acid.
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.
Xu
Guang-Lin
GL
Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, China.
Liu
Fei
F
Zhao
Yue
Y
Ao
Gui-Zhen
GZ
Xi
Liang
L
Ju
Min
M
Xue
Ting
T
D000814:Aniline Compounds / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D002109:Caffeic Acids / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D002351:Carrageenan; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D016859:Lipoxygenase Inhibitors; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000139:chemically induced
C547056:2-(4-aminophenyl)-3-(3,5-dihydroxylphenyl)propenoic acid; D000814:Aniline Compounds; D000893:Anti-Inflammatory Agents; D002109:Caffeic Acids; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D002351:Carrageenan