Selenium bioisosteric replacement of adenosine derivatives promoting adiponectin secretion increases the binding affinity to peroxisome proliferator-activated receptor δ

Peroxisome Proliferator-Activated Receptor – γ (PPARγ) is a ligand-activated transcription factor, has become a main target for the treatment of diabetes. It is a member of the nuclear receptor superfamily that regulate the gene expression of proteins involved in glucose, lipid metabolism, adipocyte proliferation and differentiation and insulin sensitivity. Thiazolidinediones (TZDs) are one important class of synthetic agonists of PPAR-γ. TZDs are antidiabetic agents that target adipose tissue and improve insulin sensitivity, and they are currently being used in the treatment of type 2 diabetes. This work was designed to find out the bioactive compounds from Momordica cymbalaria that have the ability to stimulate the PPAR-γ using molecular docking procedure. Six metabolites namely 2-Methoxy-4-vinylphenol, Guaiacol, Carbinoxamine maleate, Azulene, 4N Ethylcytosine and Methyl cinnamate were docked with PPAR-γ using AutoDock and the results were determined using binding affinity. Among the six compounds three compounds (Carbinoxamine maleate, 2-Methoxy-4-vinylphenol and 4N Ethylcytosine) showed significant binding affinity towards the PPAR-γ. Based on the findings of this study these phytochemicals can serve as source of anti-diabetic drugs via agonizing PPAR-γ.

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In silico molecular docking studies of some phytochemicals against peroxisome-proliferator activated receptor gamma (PPAR-γ)

GSC Biological and Pharmaceutical Sciences ◽

10.30574/gscbps.2018.5.2.0085 ◽

2018 ◽

Vol 5 (2) ◽

pp. 001-005

Author(s):

H. A. Ahmed ◽

I. Y. Alkali

Keyword(s):

Molecular Docking ◽

Insulin Sensitivity ◽

Binding Affinity ◽

Docking Studies ◽

Peroxisome Proliferator ◽

Autodock Vina ◽

Peroxisome Proliferator Activated Receptor ◽

Standard Drug ◽

Molecular Docking Studies ◽

Ppar Γ

Peroxisome Proliferator-Activated Receptor-γ (PPAR-γ) is a ligand-activated transcription factor and a member of the nuclear receptor superfamily that regulate the gene expression of proteins involved in glucose, lipid metabolism, adipocyte proliferation and differentiation and insulin sensitivity. Thiazolidinediones (TZDs) are one important class of synthetic agonists of PPAR-γ. TZDs are antidiabetic agents that target adipose tissue and improve insulin sensitivity, and they are currently being used in the treatment of type 2 diabetes. The study was carried out in order to discover new phytochemicals that have the ability to stimulate the PPAR-γ using molecular docking studies. AutoDock vina was used as molecular-docking tool in order to carry out the docking simulations. Nine phytochemicals namely plumbagin, quercetin, isovitexin, mangiferin, syringin, lupe-20-ene-3-one, purine 2, 6-dione, diosmetin and β sitosterol and pioglitazone a standard drug were docked against PPAR-γ using AutoDock vina and the results were analyzed using binding affinity. The results revealed that the compounds have significant binding affinity towards the PPAR-γ comparable to pioglitazone the standard drug. Based on the findings of this study these phytochemicals can serve as source of antidiabetic drugs via the mechanism of inhibition of PPAR-γ.

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Activating Effect of Benzbromarone, a Uricosuric Drug, on Peroxisome Proliferator-Activated Receptors

PPAR Research ◽

10.1155/2007/36092 ◽

2007 ◽

Vol 2007 ◽

pp. 1-5 ◽

Cited By ~ 21

Author(s):

Chiyoko Kunishima ◽

Ikuo Inoue ◽

Toshihiro Oikawa ◽

Hiromu Nakajima ◽

Tsugikazu Komoda ◽

...

Keyword(s):

Binding Affinity ◽

Cultured Cells ◽

Binding Activity ◽

Peroxisome Proliferator ◽

Peroxisome Proliferation ◽

Mobility Shift ◽

Peroxisome Proliferator Activated Receptor ◽

Western Blot Method ◽

Gene Assay ◽

Mobility Shift Assay

Benzbromarone, a uricosuric drug, reportedly causes hepatic hypertrophy accompanied by proliferation of peroxisomes in rats. To elucidate the mechanisms underlying induction of peroxisome proliferation by benzbromarone, we examined binding affinity for peroxisome proliferator-activated receptorα(PPARα) andγ(PPARγ), and effects on the binding activity of PPARs with peroxisome proliferation-responsive element (PPRE) and expression of the PPARs target protein. Binding affinity of benzbromarone forPPARαandPPARγwas examined by reporter gene assay. Binding activity of PPARs with PPRE was determined by electric mobility shift assay, and expression of lipoprotein lipase (LPL) and acyl-CoA synthetase (ACS) by Western blot method. Benzbromarone displayed affinity forPPARαandPPARγ, and promoted binding of PPARs to PPRE. Furthermore, cultured cells with benzbromarone added showed upregulated expression of LPL and ACS. These results suggest that benzbromarone induces peroxisome proliferation in hepatocytes by binding to PPARs, and controls expression of proteins related to lipid metabolism.

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