Synthesis, biological evaluation, and molecular modeling investigation of chiral 2-(4-chloro-phenoxy)-3-phenyl-propanoic acid derivatives with PPARalpha and PPARgamma agonist activity.

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Fracchiolla G, Lavecchia A, Laghezza A, Piemontese L, Trisolini R, Carbonara G, Tortorella P, Novellino E, Loiodice F

Synthesis, biological evaluation, and molecular modeling investigation of chiral 2-(4-chloro-phenoxy)-3-phenyl-propanoic acid derivatives with PPARalpha and PPARgamma agonist activity.

Bioorg Med Chem. 2008 Nov 1;16(21):9498-510. doi: 10.1016/j.bmc.2008.09.045. Epub 2008 Sep 19.

PubMed ID

18835719 [ View in PubMed

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Abstract

PPARs are ligand-activated transcription factors that govern lipid and glucose homeostasis and play a central role in cardiovascular disease, obesity, and diabetes. Herein, we present screening results for a series of chiral 2-(4-chloro-phenoxy)-3-phenyl-propanoic acid derivatives, some of which are potent PPARgamma agonists as well as PPARalpha agonists. To investigate the binding modes of the most interesting derivatives into the PPARalpha and PPARgamma binding clefts and evaluate their agonist activity, docking experiments, molecular dynamics simulations, and MM-PBSA analysis were performed.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
(2S)-2-(4-chlorophenoxy)-3-phenylpropanoic acid	Peroxisome proliferator-activated receptor gamma	EC 50 (nM)	7940	N/A	N/A	Details
Rosiglitazone	Peroxisome proliferator-activated receptor alpha	EC 50 (nM)	39	N/A	N/A	Details