Novel phenoxyalkylcarboxylic acid derivatives as hypolipidaemic agents |
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Authors: | Li Wei Jia Hao-yan He Xin-hua Shi Wei-guo Zhong Bo-hua |
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Affiliation: | Department of Pharmaceutical Chemistry, Beijing Institute of Pharmacology and Toxicology, Beijing, P.R. China. |
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Abstract: | Novel phenoxyalkylcarboxylic acid derivatives based on the natural scaffolds, flavonoids, or resveratrol were designed, synthesized, and evaluated for hypolipidaemic activity. Among the compounds, 30b lowered the triglycerides by 48.5% (P?0.05) and total cholesterol by 44.2% (P?0.05), respectively, and was more effective than the reference drug fenofibric acid in a Triton WR-1339-induced hyperlipidaemic mice model orally (300?mg/kg body weight). 30b also showed 59.4% triglycerides lowering in an alloxan-induced diabetic mice model orally (150?mg/kg body weight). Receptor docking studies revealed that compound 30b could interact with the amino acid residues in the ligand-binding domain essential for the activation of the PPARα. The results indicate that resveratrol should be a better scaffold to derive a new class of hypolipidaemic agents in comparison with a flavonoid scaffold. |
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