Identification of phytocompounds as potent inhibitors of sodium/glucose cotransporter-2 leading to diabetes treatment

Abstract

Type-II diabetes, a major metabolic disorder has threatened the very existence of a healthy life since long ago. Commercially available antidiabetic drugs are known for several adverse effects. The present study attempted to identify potential phytocompounds as inhibitors of sodium/glucose cotransporter-2 (SGLT2), a major protein that helps in glucose re-absorption from renal tubules. A total of 28 phytocompounds were collected based on the literature survey. 3D co-ordinates of phytocompounds were collected from PubChem database. Molecular docking was carried out with SGLT2 protein and the best 3 docking complexes were subjected to molecular dynamics simulation for 100 ns. Free energy changes were also analyzed using MM/PBSA analysis. Phytocompounds were also analyzed for their drug-likeness and ADMET properties. Docking study observed a strong binding affinity of phytocompounds (> −7.0 kcal/mol). More than 10 phytocompounds showed better binding affinity compared to reference drugs. Further analysis of three best docking complexes when analyzed by MD simulation showed better stability and compactness of the complexes compared to reference drug, empagliflozin. MM/PBSA analysis also revealed that van der Waals force and electrostatic energy are the major binding energy involved in the complex formation. Like docking energy, free energy analysis also observed stronger binding energies (ΔGGAS) in SGLT2-phytocompound complexes compared to empagliflozin complex. All the phytocompounds showed drug-likeness and considerable ADMET properties. The study, therefore, suggests that Trifolirhizin-6′-monoacetate, Aspalathin, and Quercetin-3-glucoside could be a possible inhibitor of SGLT2 protein. However, further studies need to be carried out to reveal the exact mode of activity.

Communicated by Ramaswamy H. Sarma

Keywords:

• Diabetes
• phytocompounds
• sodium/glucose cotransporter-2
• docking
• molecular dynamics simulation
• ADMET

Acknowledgment

Authors acknowledge the Department of Zoology, Bodoland University for providing the necessary facility to carry out the present study.

Authors contributions

AS—Design, concept, MD simulation, MM/PBSA analysis, manuscript writing, MD—drafting manuscript, AS—data collection, docking study, ADMET analysis, output visualization, AB—data collection, docking study, ADMET analysis, DB—manuscript correction & proofreading, HS—manuscript correction & proofreading.

Data availability statement

All the data required for the manuscript is within the manuscript itself. Few data are supplied as supplementary tables.

Disclosure statement

There are no conflicts of interest in this publication among the authors.

Additional information

Funding

The present study does not have any external funding.