title: Novel phenoxyalkylcarboxylic acid derivatives as hypolipidaemic agents.
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.
authors.affiliation: Department of Pharmaceutical Chemistry, Beijing Institute of Pharmacology and Toxicology, Beijing, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Hao-yan
authors.initials: HY
authors.lastname: Jia
authors.forename: Xin-hua
authors.initials: XH
authors.lastname: He
authors.forename: Wei-guo
authors.initials: WG
authors.lastname: Shi
authors.forename: Bo-hua
authors.initials: BH
authors.lastname: Zhong
mesh_terms: D000818:Animals; D002264:Carboxylic Acids / Q000737:chemistry*; D002784:Cholesterol / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D011345:Fenofibrate / Q000031:analogs & derivatives / Q000633:toxicity; D005419:Flavonoids / Q000737:chemistry; D006949:Hyperlipidemias / Q000139:chemically induced / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D011092:Polyethylene Glycols / Q000633:toxicity; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry; D013501:Surface-Active Agents / Q000633:toxicity; D014280:Triglycerides / Q000378:metabolism
chemical_list: D002264:Carboxylic Acids; D005419:Flavonoids; D000960:Hypolipidemic Agents; D013267:Stilbenes; D013501:Surface-Active Agents; D014280:Triglycerides; D011092:Polyethylene Glycols; D002784:Cholesterol; C006012:fenofibric acid; D000077185:Resveratrol; D011345:Fenofibrate; C016811:tyloxapol