title: Structure-based drug design of a novel family of chalcones as PPARalpha agonists: virtual screening, synthesis, and biological activities in vitro.
abstract: OBJECTIVE
  To design and synthesize a novel class of peroxisome proliferator-activated receptors (PPAR)alpha 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 PPARalpha agonists, compound 4 h being the most prominent with a 50% effective concentration value of 0.06 micromol/L.
  
  
  CONCLUSIONS
  This study provides a promising novel family of chalcones with a potential hypolipidemic effect.
authors.affiliation: Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Xiang-hua
authors.initials: XH
authors.lastname: Li
authors.forename: Han-jun
authors.initials: HJ
authors.lastname: Zou
authors.forename: An-hui
authors.initials: AH
authors.lastname: Wu
authors.forename: Yang-liang
authors.initials: YL
authors.lastname: Ye
authors.forename: Jian-hua
authors.initials: JH
authors.lastname: Shen
mesh_terms: D047188:Chalcones / Q000737:chemistry* / Q000494:pharmacology*; D015195:Drug Design; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D047493:PPAR alpha / Q000819:agonists*; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D047188:Chalcones; D047493:PPAR alpha