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Planta Med 2015; 81(06): 488-494
DOI: 10.1055/s-0034-1383119
Mini Reviews
Georg Thieme Verlag KG Stuttgart · New York

Identification of PPARγ Agonists from Natural Sources Using Different In Silico Approaches

Rime B. El-Houri
1   Department of Chemical Engineering, Biotechnology and Environmental Technology, University of Southern Denmark, Odense, Denmark
,
Jérémie Mortier
2   Computer-Aided Drug Design, Institute of Pharmacy, Medicinal and Pharmaceutical Chemistry, Freie Universität Berlin, Berlin, Germany
,
Manuela S. Murgueitio
2   Computer-Aided Drug Design, Institute of Pharmacy, Medicinal and Pharmaceutical Chemistry, Freie Universität Berlin, Berlin, Germany
,
Gerhard Wolber
2   Computer-Aided Drug Design, Institute of Pharmacy, Medicinal and Pharmaceutical Chemistry, Freie Universität Berlin, Berlin, Germany
,
Lars P. Christensen
1   Department of Chemical Engineering, Biotechnology and Environmental Technology, University of Southern Denmark, Odense, Denmark
› Author Affiliations
Further Information

Publication History

received 09 July 2014
revised 27 August 2014

accepted 28 August 2014

Publication Date:
24 September 2014 (online)

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Abstract

Peroxisome proliferator-activated receptor γ plays an important role in lipid and glucose homeostasis and is the target of many drug discovery investigations because of its role in diseases such as type 2 diabetes. Activation of peroxisome proliferator-activated receptor γ by agonists leads to a conformational change in the ligand-binding domain altering the transcription of several target genes involved in glucose and lipid metabolism, resulting in, for example, facilitation of glucose and lipid uptake and amelioration of insulin resistance, and other effects that are important in the treatment of type 2 diabetes. Peroxisome proliferator-activated receptor γ partial agonists are compounds with diminished agonist efficacy compared to full agonists; however, they maintain the antidiabetic effect of full agonists but do not induce the same magnitude of side effects. This mini-review gives a short introduction to in silico screening methods and recent research advances using computational approaches to identify peroxisome proliferator-activated receptor γ agonists, especially partial agonists, from natural sources and how these ligands bind to the peroxisome proliferator-activated receptor γ in order to better understand their biological effects.

Key words

PPARγ - natural products - 3D pharmacophores - in silico screening - molecular docking
 

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