In-silico anticancer potential of active constituents from “Glycyrrhiza uralensis” targeting PPAR gamma protein

Abstract

The aim of the study is to anticipate the lead molecule from the phytochemical constituents of “Glycyrrhiza uralensis” which acts on PPAR γ receptor and causes cell proliferation and inhibits cell migration in cancer disease. PyRx virtual screening (Auto docking Vina) software and Schrodinger Maestro version 11.5 were used to screen the compounds anticancer activity. Python Molecular Viewer 1.5.6 (PMV 1.5.6) was used for semi flexible docking between the chemical compounds and PPAR γ protein receptor. Schrodinger Maestro version 11.5 was used to study the molecular dynamic simulation studies. Discovery Studio 2017 R2 Client software was used for visualizing the interactions respectively. Protein receptors and chemical constituents of G. Uralensis were retrieved from Protein Data Bank (PDB) and Pubchem databases respectively. A total of 136 chemical constituents of G. Uralensis were collected from various literature databases and 67 compounds were selected for virtual screening after ADME simulations along with standard drugs. Finally, 16 compounds were taken for molecular docking process from virtual screening. Through molecular docking studies, it was identified that 12 compounds had exhibited highest binding energy than the standard compounds. We also noticed that these 12 compounds had exhibited good pIC50 values also. Molecular dynamic simulation studies also support the data obtained from the molecular dynamic studies. Successful repositioning of the analyzed compounds on to the proposed binding site confirms the drug target ability of PPAR γ. Based on the free binding energy and pIC50 values, we propose 2 compounds (Uralenin, Glabrol) as small medicinal lead compounds for further development as potent anticancer drug candidate which act by inhibiting the PPAR γ protein receptor.