Ligand-Based and Structure-Based Virtual Screening of New Sodium Glucose Cotransporter Type 2 Inhibitors

Abstract

Background: Diabetes mellitus is a metabolic disease that causes multiple complications and common comorbidities, which decreases the quality of life for people affected by the disease. Sodium glucose cotransporter type 2 (SGLT2) reabsorbs 90% of glucose in the kidneys; therefore, it is an attractive drug target for controlling blood glucose levels. Objective: The aim of this work was to obtain new potential SGLT2 inhibitors. Methods: A ligand-based virtual screening (LBVS) from the ZINC15, PubChem and ChemSpider databases using the maximum common substructure (MCS) scaffold was performed. Result: A total of 341 compounds were obtained and analyzed by molecular docking on the active site of SGLT2. Subsequently, 15 compounds were selected for molecular dynamics (MD) simulation analysis. The compounds derived from spiroketal Sa1, Sa4, and Sa9 (≤ 3.5 Å) in complex with the receptor SGLT2 showed good stability during 120 ns of MD. Conclusion: These compounds are proposed as potential SGLT2 inhibitors.

Integrative computational approaches for designing novel alpha-glucosidase inhibitors based on curculigoside A derivatives: Virtual screening, molecular docking, and molecular dynamics

“…It provides several notable benefits that significantly contribute to its extensive implementation. Ligand-based drug design, as opposed to structure-based approaches, which necessitate a comprehensive understanding of target protein structures, concentrates on the attributes and features of established ligands, which are compounds that exhibit binding affinity towards the target (11,12). Adopting this methodology has demonstrated its immense value in the quest for innovative treatments, providing a variety of advantages that augment efficacy and triumph in the process of medication development.…”