IN SILICO INVESTIGATION OF SMALLANTHUS SONCHIFOLIUS COMPOUNDS AS DPP-4 INHIBITORS FOR ANTIDIABETIC MECHANISMS

Objective: Smallanthus sonchifolius has been scientifically demonstrated to possess antidiabetic activity through the inhibition of DPP-4 in in vitro studies. However, there is still a lack of comprehensive research identifying the specific bioactive compounds responsible for this effect. This research specifically aims to explore the potential of bioactive compounds from Smallanthussonchifoliusas DPP-4 inhibitors, a known target for antidiabetic treatment, using in silico techniques. Methods: The methodologies employed in this study includedmolecular docking, ADMET prediction, and molecular dynamics simulation. The docking process was conducted on 20 test compounds against native ligands within the receptor designated by code 3G0B, as well as against comparative compounds. Results: Molecular docking analysis revealed four compounds—3,4-dicaffeoylquinic acid, Nystose, 1,3-O-dicaffeoylquinic acid, and 3,5-caffeoylquinic acid-that exhibited lower rerank scores than the positive control, alogliptin. Further investigation through molecular dynamics simulations demonstrated that the Nystose-ligand complex displayed stable binding dynamics similar to alogliptin, maintaining consistent interactions throughout the simulation. Key amino acid residues, including Glu205, Glu206, Ser209, Tyr547, Tyr662, and Ser630, were involved in critical hydrogen bonding, contributing to the stability of the Nystose complex. However, despite its promising binding profile, Nystose is predicted to have limited intestinal absorption due to the high number of polar substituents, which may impact its bioavailability. Conclusion: Nystose is predicted to act as a DPP-4 inhibitor for diabetes treatment based on findings from molecular docking and molecular dynamics simulations.