Yadav Jyoti, Ahsan Farogh, Panda Prabhudatta, Mahmood Tarique, Bano Shahzadi, Shamim Arshiya, Mishra Pooja
Department of Pharmacy, Integral University, Dasauli, Kursi Road, Lucknow (U.P.), 226026, India.
Department of Pharmacy, Institute of Technology & Management, Gorakhpur (U.P.), 273209, India.
Cardiovasc Hematol Disord Drug Targets. 2024;24(4):254-265. doi: 10.2174/011871529X341930241206063315.
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.
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.
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 analysis conducted in this study examines the binding free energy values of Empagliflozin with key target proteins.
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.
These findings offer valuable insights into the therapeutic possibilities of Empagliflozin in cardioprotection, indicating promising avenues for further research and development in this domain.
药物重新利用涉及研究已获批用于临床的药物的新适应症或用途。恩格列净是一种C-糖基化合物，其特征在于存在β-葡萄糖基残基。它作为钠-葡萄糖协同转运蛋白2抑制剂发挥作用，用于改善被诊断为2型糖尿病的成年人的血糖控制。此外，它还适用于降低患有2型糖尿病和已有心血管疾病的成年患者的心血管死亡风险。
该研究的目标是通过计算方法探索一种名为恩格列净的新型SGLT2抑制剂作为抗糖尿病药物的重新利用潜力，特别关注其与心脏保护关键靶蛋白的相互作用。
通过使用Autodock将恩格列净与不同的靶蛋白（NHE1-CHP1、BIRC5、GLUT1和XIAP）进行对接来开展该研究，并记录不同的值。对接文件由BIOVIA Discovery Studio Visualizer进行分析。本研究中进行的分析考察了恩格列净与关键靶蛋白的结合自由能值。
结果显示，NHE1-CHP1的结合自由能最低，其次是BIRC5、GLUT1和XIAP，后者的值最高。这种结合能的降序表明在结合分子方面有效性程度不同，较低的能量表明更强的生物活性。该分析强调了分子间相互作用的重要性，特别是化合物结构中的氧、氮和羰基促进的氢键形成。值得注意的是，与其他靶蛋白相比，NHE1-CHP1与恩格列净表现出更好的结合相互作用，突出了其作为心脏保护剂的潜力。
这些发现为恩格列净在心脏保护方面的治疗可能性提供了有价值的见解，表明该领域有前景的进一步研究和开发途径。
