Structure-based drug design of a novel family of chalcones as PPARalpha agonists: virtual screening, synthesis, and biological activities in vitro.
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.
Li
Xiang-hua
XH
Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Zou
Han-jun
HJ
Wu
An-hui
AH
Ye
Yang-liang
YL
Shen
Jian-hua
JH
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
D047188:Chalcones; D047493:PPAR alpha