| Summary: | 碩士 === 高雄醫學大學 === 藥學研究所 === 88 === For a continued study of structure-activity relationship of various chalcone derivatives designed as anti-inflammatory agents, we have synthesized a series of new chalcone derivatives and related compounds, 1-11, and studied on their anti-inflammatory effects.
All the chalcones and related compounds were prepared by Claisen- Schmidt Condensation of appropriate acetophenones with appropriate aromatic aldehydes. Alkoxylchalcones were prepared by appropriate dihydroxylchalcones and alkyl iodides. One flavone was synthesized by appropriate acetophenone with benzoyl chloride through Baker- Venkataraman rearrangement. The anti-inflammatory activities of these synthetic compounds were studied on inhibitory effects on the activation of mast cells, neutrophils, macrophages and microglial cells.
Chalcones, 3, 4, 6, 8, showed strong inhibitory effects on the release of β-glucuronidase and histamine from rat peritoneal mast cells stimulated with compound 48/80. Chalcones, 1, 2, 3, 4, 6, 8, exhibited potent inhibitory effects on the release of β-glucuronidase and lysozyme from rat neutrophils stimulated with formyl-Met-Leu-Phe (fMLP). Chalcones, 1, 2, 3, 4, 6, 10, showed potent inhibitory effects on superoxide formation of rat neutrophils stimulated with fMLP/cytochalasin B(CB) while 8 indicated weak inhibitory effects on superoxide formation of rat neutrophils stimulated with phorbol myristate acetate(PMA). Compounds 1 and 5, alkoxychalcones, exhibited potent inhibitory effects on nitric oxide (NO) formation from macrophage like cell line RAW 264.7 cells stimulated with lipopolysaccharide (LPS) and murine microglial cell line N9 stimulated with LPS/interferon (IFN)-γrespectively. Compound 11, a flavone, showed distinctively inhibitory effects on tumor necrosis factor (TNF)-α formation from N9 cell line caused by LPS/ IFN-γ.
The present results demonstrated most of the chalcone derivatives have anti-inflammatory effects. The inhibitory effects of these compounds on inflammation are partly mediated through the suppression of chemical mediators released from mast cells and neutrophils. The inhibitory effects of dialkoxychalcones on inflammation are probably not only due to the inhibition of mast cells and neutrophils degranulation, but also are mediated partially through the suppression of NO formation from N9 cell. These findings suggested that some chalcones might probably have beneficial effects on the central neurodegenerative disorders observed in aging and Alzheimer’s disease.
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