Drugs repurposing for heart failure – computational approaches targeting SGLT2
Abstract
SGLT2 (Abstract): Sodium-glucose co-transporter 2 (SGLT2) inhibitors are the latest approved treatment for heart failure (HF), demonstrating a significant reduction in cardiovascular outcomes associated with this condition.Based on the increasing prevalence of HF and the urgent demand for safer and more effective therapeutic options, this study employed in silico approaches to systematically screen a comprehensive library of conventional drugs for their binding affinity to the SGLT2 protein.Materials and methods: More than 70 drugs, belong to several chemical and pharmacological classes, such as proton pump inhibitors, oral hypoglycemic drugs (sulfonylureas, gliptins), statins, nonsteroidal anti-inflammatory drugs, H 1 /H 2 antagonists, antineoplastic drugs, alfa-adrenergic agonists, vitamins, antioxidants, were screened for their SGLT2 affinity using m olecular docking method.In addition, for the drugs with the best docking score, a pharmacokinetic profile prediction using computational tools was also performed.Canagliflozin, empagliflozin and dapagliflozin were used as SGLT2 reference inhibitors.Results and discussion: The docking simulations revealed that the binding of the ligands to SGLT2 involves direct hydrogen bonds and van der Waals interactions with amino acids in the active site, such as H80, G83, L84, F98, E99, V85, V157, K154, L283, V286, V287, Y290, W291 and Q457.The best docking sc ore, much better than SGLT2 reference inhibitors, was obtained for…
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