In silico discovery of potential sodium-glucose cotransporter-2 (SGLT-2) inhibitors from Smallanthus sonchifolius (Poepp.) H.Rob. via molecular docking and molecular dynamics simulation approach
Abstract
Context: Smallanthus sonchifolius or yacon has been reported to have hypoglycemic effects. Inhibition of sodium-glucose cotransporter 2 (SGLT-2) is one of the mechanisms of antidiabetic drugs.
Aims: To evaluate potential compounds in S. sonchifolius as SGLT-2 inhibitors using molecular docking analysis and dynamic simulation, as well as predict the pharmacokinetic profiles of the potent compounds using ADMETlab 3.0.
Methods: Fourteen molecules from S. sonchifolius were docked with SGLT-2 (PDB Code 7VSI) simultaneously as empagliflozin and canagliflozin as standard ligands. Three compounds, they are 3,5-dicaffeoylquinic acid (3,5-DCQA); and 3,4-dicaffeoylquinic acid (3,4-DCQA), 1-kestose, showed lower rerank scores than empagliflozin and canagliflozin. The analysis proceeded to molecular dynamic simulation by investigating the RMSD and binding energy of SGLT-2 protein in complexes with the ligands to evaluate the dynamic behavior of protein-ligand complexes.
Results: All ligands illustrate similar patterns with two ligand controls, suggesting its acceptable movement from the binding site of SGLT-2. 1-Kestose exhibited stronger binding affinity with SGLT-2 during the period of simulation and continued to interact with the binding pocket of SGLT-2 until the end of the simulation, which involved some critical residues, including Phe98, Glu99, and Ser287, and mainly contributed to hydrogen bond interactions. However, 1-kestose was predicted to have low gastrointestinal absorption…
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