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Drug Des Devel Ther. 2015 Nov 4;9:5877-95. doi: 10.2147/DDDT.S93449. eCollection 2015.

In silico approach for the discovery of new PPARγ modulators among plant-derived polyphenols.

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Molecular and Cell Biology Institute, Miguel Hernández University, Elche, Spain.
Physics and Computer Architecture Department, Miguel Hernández University, Elche, Spain.
Molecular and Cell Biology Institute, Miguel Hernández University, Elche, Spain ; CIBER: CB12/03/30038 Physiopathology of Obesity and Nutrition, CIBERobn, Instituto de Salud Carlos III, Palma de Mallorca, Spain.


Peroxisome proliferator-activated receptor gamma (PPARγ) is a well-characterized member of the PPAR family that is predominantly expressed in adipose tissue and plays a significant role in lipid metabolism, adipogenesis, glucose homeostasis, and insulin sensitization. Full agonists of synthetic thiazolidinediones (TZDs) have been therapeutically used in clinical practice to treat type 2 diabetes for many years. Although it can effectively lower blood glucose levels and improve insulin sensitivity, the administration of TZDs has been associated with severe side effects. Based on recent evidence obtained with plant-derived polyphenols, the present in silico study aimed at finding new selective human PPARγ (hPPARγ) modulators that are able to improve glucose homeostasis with reduced side effects compared with TZDs. Docking experiments have been used to select compounds with strong binding affinity (ΔG values ranging from -10.0±0.9 to -11.4±0.9 kcal/mol) by docking against the binding site of several X-ray structures of hPPARγ. These putative modulators present several molecular interactions with the binding site of the protein. Additionally, most of the selected compounds have favorable druggability and good ADMET properties. These results aim to pave the way for further bench-scale analysis for the discovery of new modulators of hPPARγ that do not induce any side effects.


ADMET; AutoDock/Vina; TZDs; high-throughput computing; human PPARγ; molecular docking; phenolic compounds; virtual screening

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