TY - JOUR AU - FARKHANI, AULIA AU - SAURIASARI, RANI AU - YANUAR, ARRY PY - 2020/03/23 Y2 - 2024/03/29 TI - IN SILICO APPROACH FOR SCREENING OF THE INDONESIAN MEDICINAL PLANTS DATABASE TO DISCOVER POTENTIAL DIPEPTIDYL PEPTIDASE-4 INHIBITORS JF - International Journal of Applied Pharmaceutics JA - Int J App Pharm VL - 12 IS - 1 SE - Original Article(s) DO - 10.22159/ijap.2020.v12s1.FF008 UR - https://journals.innovareacademics.in/index.php/ijap/article/view/37536 SP - 60-68 AB - <p><strong>Background</strong>: Dipeptidyl peptidase-4 (DPP4) is an enzyme responsible for inactivating the hormone incretin, which potentiates insulin secretion and<br>glucagon inhibition; inhibitors of DPP4 are used as therapeutic drugs for type-2 diabetes.<br><strong>Objective</strong>: In this study, we evaluated potential DPP4 inhibitors from the Indonesian Medicinal Plants Database using an in silico approach.<br><strong>Methods</strong>: A ligand-based pharmacophore model was used for screening the database using LigandScout 4.2. This model was validated using several<br>parameters of enrichment metrics, including receiver operating characteristics, area under curve (AUC), and enrichment factor (EF). Hit compounds<br>were also docked with DPP4 to calculate the free binding energy and analyze the interaction between the ligand and DPP4. In addition, bioavailability<br>and medicinal chemistry predictions were performed for the hit compounds.<br><strong>Results</strong>: The best pharmacophore model demonstrated AUC100% and EF1% values of 0.82 and 33.8, respectively. The pharmacophore features of the<br>model included hydrogen bond donors, hydrogen bonds, hydrophobic interactions, and positive ionization areas. Based on our results of virtual<br>screening and molecular docking, six hit compounds were ultimately identified, namely, L-noradrenaline, octopamine, Nb-demethylechitamine, alliin,<br>isoalliin, and subaphylline.<br><strong>Conclusion</strong>: Collectively, our findings indicate that subaphylline is the most promising compound for further studies, including in vitro and in vivo<br>experiments and those focused on molecular dynamics and structural modification.</p> ER -