Title:Ligand-Based and Structure-Based Virtual Screening of New Sodium
Glucose Cotransporter Type 2 Inhibitors
Volume: 19
Issue: 10
Author(s): Ana Karen Estrada, Domingo Mendez-Alvarez, Alfredo Juarez-Saldivar, Edgar E. Lara-Ramirez, Ana Veronica Martinez-Vazquez, Juan Carlos Villalobos-Rocha, Isidro Palos, Eyra Ortiz-Perez and Gildardo Rivera*
Affiliation:
- Laboratorio de Biotecnologia Farmaceutica, Centro de Biotecnologia Genomica, Instituto Politecnico Nacional, 88710
Reynosa, Mexico
Keywords:
Diabetes mellitus, inhibitors, molecular docking, maximum common substructure, SGLT2, blood glucose.
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) participates in the reabsorption of 90% of glucose in
the kidneys; therefore, it is an attractive drug target for controlling blood glucose levels.
Objective: The aim in 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 of 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.