Structure-based drug design of a novel family of chalcones as PPARα agonists: virtual screening, synthesis, and biological activities in vitro
Authors: LI, Xiang-hua; ZOU, Han-jun; WU, An-hui; YE, Yang-liang; SHEN, Jian-hua
Source: Acta Pharmacologica Sinica, Volume 28, Number 12, December 2007 , pp. 2040-2052(13)
Aim: To design and synthesize a novel class of peroxisome proliferator-activated receptors (PPAR)α agonists, which is obtained by the combination of the classical fibrate “head group”, a linker with appropriate length and a chalcone. Methods: Thirty seven compounds were designed and identified employing the virtual screening approach. Six compounds were then selected for synthesis and bioassay according to the virtual screening results, structural similarity, and synthetic complexity. Results: Six new compounds (4b and 4d-h) were synthesized and bioassayed. All were found to be potent PPARα agonists, compound 4 h being the most prominent with a 50% effective concentration value of 0.06 mol/L. Conclusion: This study provides a promising novel family of chalcones with a potential hypolipidemic effect.
Document Type: Research Article
Affiliations: Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
Publication date: December 2007