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Synthesis, Anti-inflammatory Activities and Mechanisms of 3,5- dihydroxycinnamic Acid Derivatives.
- Source :
-
Anti-inflammatory & anti-allergy agents in medicinal chemistry [Antiinflamm Antiallergy Agents Med Chem] 2015; Vol. 14 (3), pp. 183-98. - Publication Year :
- 2015
-
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.<br />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.<br />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.<br />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.
- Subjects :
- Animals
Arachidonate 5-Lipoxygenase metabolism
Arachidonic Acid
Calcimycin pharmacology
Cell Line
Cell Line, Tumor
Cell Survival drug effects
Cyclooxygenase 2 metabolism
Cytokines genetics
Cytokines immunology
Dinoprostone metabolism
Ear pathology
Edema chemically induced
Edema drug therapy
Edema immunology
Edema pathology
Female
Lipopolysaccharides
Mice, Inbred BALB C
Peroxidase immunology
RNA, Messenger metabolism
Rats
Tetradecanoylphorbol Acetate
Anti-Inflammatory Agents chemical synthesis
Anti-Inflammatory Agents pharmacology
Anti-Inflammatory Agents therapeutic use
Cinnamates chemical synthesis
Cinnamates pharmacology
Cinnamates therapeutic use
Lipoxygenase Inhibitors chemical synthesis
Lipoxygenase Inhibitors pharmacology
Lipoxygenase Inhibitors therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1875-614X
- Volume :
- 14
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Anti-inflammatory & anti-allergy agents in medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 26712249
- Full Text :
- https://doi.org/10.2174/1871523015666151229101438