In-silico analysis for the confirmation of insulin receptor as a target for reported GLUT4 anti-diabetic natural compounds
1 Department of Science Laboratory Technology, Faculty of Sciences, Federal Polytechnic, Kaltungo-770117, Gombe State, Nigeria.
2 Biological Sciences Department of Biological Sciences Indian Institute of Science Education and Research, Berhampur, Odisha-760010, India.
3 School of Pharmacy, Dr. Vishwanath Karad MIT World Peace University, Pune-411038, Maharashtra, India.
4 Department of Biophysics, Molecular Biology and Bioinformatics, University of Calcutta, Kolkata-700073, India.
5 Department of Biosciences MES College, Marampally Aluva, Kerala-683107, India.
6 School of Chemistry and Chemical Engineering, University of Jinan, Jinan-250022, PR China.
7 Department of Biochemistry, Faculty of Pharmacy, University of Santo Tomas, Sampaloc, Manila-1008, Philippines.
8 Research Center of Natural and Applied Sciences, University of Santo Tomas, Sampaloc, Manila-1008, Philippines.
9 Bioshack India Pvt. Ltd., New Delhi- 110001, India.
10 School of Biological Sciences, University of Portsmouth, Street Portsmouth PO1 2DY, England.
# All the authors contributed equally and should be considered as first authors
Research Article
GSC Biological and Pharmaceutical Sciences, 2022, 19(02), 205–214.
Article DOI: 10.30574/gscbps.2022.19.2.0190
Publication history:
Received on 12 April 2022; revised on 15 May 2022; accepted on 18 May 2022
Abstract:
Purpose of Research: There are 425 million people with diabetes in the World. There will be 629 million people with diabetes in the World in 2045. The insulin receptor controls glucose homeostasis, a physiological mechanism that can lead to diabetes and cancer if disrupted.
Scope of The Experiments: This study aimed to confirm the Insulin Receptor target for reported GLUT4 anti-diabetic natural compounds based on their pharmacokinetic properties, toxicity prediction, molecular docking, target analysis, similar FDA approved drugs prediction, and molecular dynamic simulation. We selected 24 compounds on the basis of their mode of action from the anti-diabetic natural compounds database (ADNCD). Initially, we performed ADME analysis for the selected 24 compounds.
Results: Among these 24 compounds, it has been found that 18 compounds followed the Lipinski Rule of Five. Further, we did a toxicity analysis of those 18 compounds, and it was found that 15 compounds were toxic in nature. We performed molecular docking against the Insulin Receptor (PDB ID: 1IR3) of the rest of the 3 compounds after ADME and toxicity analysis. To understand the dynamic motions of the ligand-protein complex, we perform a root mean square fluctuation analysis. We also checked the similarity of Apigenin from the FDA-approved drugs, but no similar molecule was found.
Findings and Conclusions: It has been found that Apigenin was selected as the best compound as it showed the lowest binding energy and satisfied all our study parameters. Our promising findings based on preliminary and in-silico analysis need to be validated further by in-vitro and in-vivo studies.
Keywords:
Insulin Receptor; Anti-Diabetic Natural Compounds; ADME; Toxicity; Molecular Docking; Swisssimilarity
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