Novel phenoxyalkylcarboxylic acid derivatives as hypolipidaemic agents

Author： Li Wei Jia Hao-yan He Xin-hua Shi Wei-guo Zhong Bo-hua

ISSN： 1475-6366

Source： Journal of Enzyme Inhibition and Medicinal Chemistry, Vol.27, Iss.2, 2012-04, pp. : 311-318

Disclaimer: Any content in publications that violate the sovereignty, the constitution or regulations of the PRC is not accepted or approved by CNPIEC.

Previous Menu Next

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.