Identification of potential antidiabetic inhibitor from Mimosa pudica Linn. through in silico molecular modeling and DFT tools

Identification of potential antidiabetic inhibitor from Mimosa pudica Linn. through in silico molecular modeling and DFT tools Chandrasekar Palanichamy Department of Biotechnology, Kalasalingam Academy of Research and Education Parasuraman Pavadai Department of Pharmaceutical Chemistry, Faculty of Pharmacy, M.S. Ramaiah University of Applied Sciences Panneerselvam Theivendren Department of Pharmaceutical Chemistry & Analysis, School of Pharmaceutical Sciences, Vels Institute of Science, Technology & Advanced Studies Madasamy Sundar Department of Biotechnology, Kalasalingam Academy of Research and Education Alagarsamy Santhana Krishna Kumar Department of Chemistry, National Sun Yat-sen University Selvaraj Kunjiappan Department of Biotechnology, Kalasalingam Academy of Research and Education

Presently prescribed synthetic antidiabetic drugs effectively manage type 2 diabetes mellitus (T2DM) and, at the same time, cause severe toxic side effects. Generating novel molecules is significantly hampered by their longer time and insufficient physicochemical, pharmacokinetic, and intrinsic properties. In this view, a potential antidiabetic inhibitor from Mimosa pudica L. can be identified via in silico molecular modeling and Density Functional Theory (DFT) tools for effi-ciently managing T2DM with minimal side effects. Primarily, we evaluated the network analysis to observe the genes, proteins, and enzymes contributing to the signaling network of Peroxisome proliferator-activated receptors (PPARs) family proteins and identified PPARγ as a potential antidiabetic receptor protein. Thirty-six bioactive molecules were picked from M. pudica L. ethanolic extract through LC-MS and GC-MS analysis of our previous study report. Based on the pilot study, the selected molecule’s structure was drawn using Chemsketch software and docked against the PPARγ receptor. Interestingly, three high-scoring molecules were observed, namely, apigetrin (-8.6 kcal/mol), orientin ( 8.5 kcal/mol), isoquercetin (-8.3 kcal/mol), whereas compared to standard reference drug pioglitazone (-8.3 kcal/mol). In addition, molecular dynamics (MD) simulation research to discover intermolecular interactions and the stability of protein-ligand complexes. The in silico ADME&T studies displayed that apigetrin showed drug-like behaviours and less toxic effects. Further, MD simulation studies established the stability of apigetrin and orientin with the PPARγ protein binding pockets. According to these discoveries, the top-scored molecule, apigetrin, might be used as a potential antidiabetic inhibitor and can be used as a new optional medicine for the therapy of T2DM.
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