Evaluation of endogenous fatty acid amides and their synthetic analogues as potential anti-inflammatory leads
| Autor: | Hung The Dang, Gyeoung Jin Kang, Eun Sook Yoo, Jongki Hong, Jae Sue Choi, Hyung Sik Kim, Hae Young Chung, Jee H. Jung |
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| Rok vydání: | 2011 |
| Předmět: |
Chemokine
Stereochemistry Clinical Biochemistry Anti-Inflammatory Agents Pharmaceutical Science Nitric Oxide Biochemistry Cell Line Mice chemistry.chemical_compound Drug Discovery Animals Humans Molecular Biology chemistry.chemical_classification biology Fatty Acids Organic Chemistry Fatty acid Amides In vitro Amino acid HaCaT chemistry biology.protein Molecular Medicine Amine gas treating Enone Polyunsaturated fatty acid |
| Zdroj: | Bioorganic & Medicinal Chemistry. 19:1520-1527 |
| ISSN: | 0968-0896 |
| Popis: | A series of endogenous fatty acid amides and their analogues (1-78) were prepared, and their inhibitory effects on pro-inflammatory mediators (NO, IL-1β, IL-6, and TNF-α) in LPS-activated RAW264.7 cells were evaluated. Their inhibitory activity on the pro-inflammatory chemokine MDC in IFN-γ-activated HaCaT cells was also examined. The results showed that the activity is strongly dependent on the nature of the fatty acid part of the molecules. As expected, the amides derived from enone fatty acids showed significant activity and were more active than those derived from other types of fatty acids. A variation of the amine headgroup also altered bioactivity profile remarkably, possibly by modulating cell permeability. Regarding the amine part of the molecules, N-acyl dopamines exhibited the most potent activity (IC(50) ∼2 μM). This is the first report of the inhibitory activity of endogenous fatty acid amides and their analogues on the production of nitric oxide, cytokines (IL-1β, IL-6, and TNF-α) and the chemokine MDC. This study suggests that the enone fatty acid-derived amides (such as N-acyl ethanolamines and N-acyl amino acids) and N-acyl dopamines may be potential anti-inflammatory leads. |
| Databáze: | OpenAIRE |
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