Repurposing of Empagliflozin as Cardioprotective Drug: An in-silico Approach.

Abstract

Background: Drug repurposing involves investigating new indications or uses for drugs that have already been approved for clinical use. Empagliflozin is a C-glycosyl compound characterized by the presence of a beta-glucosyl residue. It functions as a sodium-glucose co-transporter 2 inhibitor and is utilized to enhance glycemic control in adults diagnosed with type 2 diabetes mellitus. Additionally, it is indicated for the reduction of cardiovascular mortality risk in adult patients who have both type 2 diabetes mellitus and pre-existing cardiovascular disease.

Objective: The study's objective revolves around exploring the repurposing potential of a novel SGLT2 inhibitor acting as an antidiabetic drug named Empagliflozin through computational methods, with a specific focus on its interaction with cardioprotective key target proteins.

Methods: The study was performed by docking the empagliflozin with different target proteins (NHE1- CHP1, BIRC5, GLUT1, and XIAP) by using Autodock, and different values were recorded. The docked files were analysed by the BIOVIA Discovery Studio Visualizer. The in silico analysis conducted in this study examines the binding free energy values of Empagliflozin with key target proteins.

Results: Results revealed that NHE1-CHP1 exhibits the lowest binding free energy, followed by BIRC5, GLUT1, and XIAP, with the highest value. This descending order of binding energies suggests varying degrees of effectiveness in binding molecules, with lower energies indicative of more potent biological activity. The analysis underscores the importance of intermolecular interactions, particularly hydrogen bond formations facilitated by oxygen, nitrogen, and carbonyl groups in compound structures. Notably, NHE1-CHP1 demonstrates superior binding interactions with Empagliflozin compared to the other target proteins, highlighting its potential as a cardioprotective agent.

Conclusion: These findings offer valuable insights into the therapeutic possibilities of Empagliflozin in cardioprotection, indicating promising avenues for further research and development in this domain.