Identification of Novel Drug-Like Compounds from Momordica cymbalaria as PPAR-γ Agonists: A Molecular Docking Study
DOI:
https://doi.org/10.51983/ajeat-2019.8.2.1135Keywords:
Momordica cymbalaria, PPAR-γ, Anti-diabetic activity, Molecular dockingAbstract
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.
References
E. Ozturk, A.K.K. Arslan, M.B. Yerer, and A. Bishayee, "Resveratol and diabetes: a critical review of clinical studies," Biomed. Pharmacother., vol. 5, pp. 230-234, 2017.
J.H. He, L.X. Chen, and H. Li, "Progress in the discovery of naturally occurring anti-diabetic drugs and in the identification of their molecular targets," Fitoterapia, vol. 134, pp. 270–289, 2019.
E. Z. Tenenbaum, E. Z. Fisman, and M. Motro, "Metabolic syndrome and type 2 diabetes mellitus: focus on peroxisome proliferator activated receptors (PPAR)," Cardiovascular diabetology, vol. 2, no. 1, pp. 4, 2003.
R. Jeyadevi, T. Sivasudha, A. Rameshkumar, B. Sangeetha, D. Arul Ananth, and G. Smilin Bell Aseervatham, "Nutritional constituents and medicinal values of Momordica cymbalaria (Athalakkai) – A review," Asian Pac J Trop Biomed., pp. S456-S461, 2012.
H.Y. Hung, K. Qian, S.L. Morris-Natschke, C.S. Hsu, and K.H. Lee, "Recent discovery of plant-derived anti-diabetic natural products," Nat. Prod. Rep., vol. 2, no. 5, pp. 580-606, 2012.
E. Abbirami, L. Dinesh Kumar, R. Guna, N. Gayathri, and T. Sivasudha, "Alpha amylase, alpha glucosidase inhibition and profiling of volatile compounds of biologically active extracts from Momordica cymbalaria (Hook, Fenzl) skin and seeds," AJEAT, vol. 8, no. 1, pp. 67-73, 2019.
G.R. Bickerton, G.V. Paolini, J. Besnard, S. Muresan, and A.L. Hopkins, "Quantifying the chemical beauty of drugs," Nat. Chem., vol. 4, no. 2, p. 90, 2012.
J. Ma, S. Wang, F. Zhao, and J. Xu, "Protein threading using context-specific alignment potential," Bioinformatics., vol. 29, no. 13, pp. 257-265, 2013.
M. Kallberg, H. Wang, S. Wang, J. Peng, Z. Wang, H. Lu, and J. Xu, "Template-based protein structure modeling using the RaptorX web server," Nature protocols., vol. 7, no. 8, pp. 1511, 2012.
J. Ma, J. Peng, S. Wang, and J. Xu, "A Conditional Nueral Fields model for protein threading," Bioinformatics, vol. 28, no. 12, pp. 59–66, 2012.
M.A. Lee, L. Tan, H. Yang, Y.G. Im, and Y.J. Im, "Structures of PPARγ complexed with lobeglitazone and pioglitazone reveal key determinants for the recognition of antidiabetic drugs," Scientific reports., vol. 7, no. 1, pp. 16837, 2017.
L. Wang, B. Waltenberge, and E.M. Pferschy-Wenzig, "Natural product agonists of peroxisome proliferator-activated receptor gamma (PPARgamma): a review," BiochemPharmacol., vol. 92, no. 1, pp. 73-89, 2014.
S. Prabhu, S. Vijayakumar, P. Manogar, G.P. Maniam, and N. Govindan, "Homology modeling and molecular docking studies on Type II diabetes complications reduced PPARγ receptor with various ligand molecules," Biomed. Pharmacother., vol. 92, pp. 528-535, 2017.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2019 The Research Publication
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.