Andri Prasetiyo, Esti Mumpuni, Dewi Luthfiana, Rina Herowati, Galih Satrio Putra
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 due to many polar substituents, while 3,4-DCQA and 3,5-DCQA have higher gastrointestinal absorption. Conclusions: One phytochemical present in S. sonchifolius is 1-kestose, which is thought to have action as an SGLT-2 inhibitor for the treatment of diabetes based on the findings of molecular docking and molecular dynamics investigations. This compound falls into BCS Class III, which means it has good solubility but poor permeability. © 2025 Journal of Pharmacy & Pharmacognosy Research.
Faculty of Pharmacy, Pancasila University, Jakarta, Indonesia; Graduate School of Bioagricultural Sciences, Department of Applied Biosciences, Nagoya University, Japan; Bioinformatics Research Center, Indonesian Institute of Bioinformatics (INBIO), Malang, Indonesia; Faculty of Pharmacy, Setia Budi University, Surakarta, Indonesia; Department of Chemistry, Faculty of Mathematics and Natural Sciences, State University of Malang, Indonesia
