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Biological Evaluation of 2‐(4‐Amino‐Phenyl)‐3‐(3,5‐Dihydroxylphenyl) Propenoic Acid
Author(s) -
Xu GuangLin,
Liu Fei,
Zhao Yue,
Ao GuiZhen,
Xi Liang,
Ju Min,
Xue Ting
Publication year - 2009
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/j.1742-7843.2009.00463.x
Subject(s) - cyclooxygenase , pharmacology , in vivo , in vitro , resveratrol , enzyme , chemistry , arachidonate 5 lipoxygenase , enzyme inhibitor , lipoxygenase , inflammation , medicine , biochemistry , biology , immunology , arachidonic acid , microbiology and biotechnology
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 μM, COX‐2 IC 50 = 1.76 μM) and 5‐LOX (IC 50 = 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.