Synthesis, Anti-inflammatory Activities and Mechanisms of 3,5- dihydroxycinnamic Acid Derivatives

Author(s): Meng-Jun Zhang, Juan Zhou, Wen Cao, Zhi-Qiang Feng, Jia-Wei Guo, Qing-Juan Han, Wen-Xuan Cao, Xiao Guan, Yun-Yun Li, Jianbo Qin, Yu Wang, Hui-Jing Zhang, Bin Li.

Journal Name: Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry

Volume 14 , Issue 3 , 2015

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Abstract:

Background: 3,4-dihydroxycinnamic acid and its derivatives exhibit numerous biologic activities. Such activities have not previously been reported for 3,5-dihydroxycinnamic acid derivatives. In this study, ten derivatives of 3,5- dihydroxycinnamic acid were synthesized and their anti-inflammatory activities were tested in 12-O-tetradecanoylphorbol 13-acetate-induced mouse ear edema. Molecular biological studies have shed lights on their anti-inflammatory mechanism.

Methods: Anti-inflammatory activities of ten new synthesized derivatives of 3,5-dihydroxycinnamic acid were tested in 12-O-tetradecanoylphorbol 13-acetate-induced mouse ear edema, and their anti-inflammatory mechanism was studied by ELISA, real-time RT-PCR, MPO assay and AA-induced mouse ear edema.

Results: Compound 7 showed a pronounced anti-inflammatory effect and the inhibition rate was 65.6% at a dose of 1.6mg/ear. This compound acted by reducing mRNA and protein synthesis of tumor necrosis factor-α, interleukins 1β and 6, and also by decreasing the levels of activated neutrophil infiltrates. Furthermore, compound 7 significantly suppressed arachidonic acid-induced edema as well. Cell-based assays showed that compound 7 inhibited the production of cyclooxygenase- 2-catalyzed prostaglandin E2 from lipopolysaccharide-treated RAW 264.7 cells, and also inhibited 5-lipoxygenase production from A23187-treated RBL-1 cells, and consequently reduced leukotriene B4 production.

Conclusion: This investigation revealed that some of the derivatives of 3,5-dihydroxycinnamic acid exhibit a more pronounced anti-inflammatory effect than 3,4-dihydroxycinnamic acid. Therefore, 3,5-dihydroxycinnamic acid derivatives, especially compound 7, represent potential value for antiinflammatory drug development.

Keywords: AA-induced ear edema, anti-inflammatory effect, 3, 5-dihydroxycinnamic acid derivatives, 3, 4-dihydroxycinnamic acid, proinflammatory cytokines, TPA-induced ear edema.

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Article Details

VOLUME: 14
ISSUE: 3
Year: 2015
Page: [183 - 198]
Pages: 16
DOI: 10.2174/1871523015666151229101438
Price: $58

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