IN SILICO APPROACH FOR SCREENING OF THE INDONESIAN MEDICINAL PLANTS DATABASE TO DISCOVER POTENTIAL DIPEPTIDYL PEPTIDASE-4 INHIBITORS

Background: Dipeptidyl peptidase-4 (DPP4) is an enzyme responsible for inactivating the hormone incretin, which potentiates insulin secretion andglucagon inhibition; inhibitors of DPP4 are used as therapeutic drugs for type-2 diabetes.Objective: In this study, we evaluated potential DPP4 inhibitors from the Indonesian Medicinal Plants Database using an in silico approach.Methods: A ligand-based pharmacophore model was used for screening the database using LigandScout 4.2. This model was validated using severalparameters of enrichment metrics, including receiver operating characteristics, area under curve (AUC), and enrichment factor (EF). Hit compoundswere also docked with DPP4 to calculate the free binding energy and analyze the interaction between the ligand and DPP4. In addition, bioavailabilityand medicinal chemistry predictions were performed for the hit compounds.Results: The best pharmacophore model demonstrated AUC100% and EF1% values of 0.82 and 33.8, respectively. The pharmacophore features of themodel included hydrogen bond donors, hydrogen bonds, hydrophobic interactions, and positive ionization areas. Based on our results of virtualscreening and molecular docking, six hit compounds were ultimately identified, namely, L-noradrenaline, octopamine, Nb-demethylechitamine, alliin,isoalliin, and subaphylline.Conclusion: Collectively, our findings indicate that subaphylline is the most promising compound for further studies, including in vitro and in vivoexperiments and those focused on molecular dynamics and structural modification