Comparative Molecular Docking and ADMET Analysis of Bioactive Compounds from Curcuma xanthorrhiza and Momordica charantia as Potential DPP-4 Inhibitors
DOI:
https://doi.org/10.62872/o.v3i1.511Keywords:
DPP-4 inhibitor, molecular docking, ADMET, natural compounds, type 2 diabetes mellitusAbstract
Background: Type 2 Diabetes Mellitus (T2DM) is characterized by impaired insulin secretion and insulin resistance. Dipeptidyl Peptidase-4 (DPP-4) regulates glucose homeostasis by degrading incretin hormones such as GLP-1, making it a key therapeutic target. Natural bioactive compounds from Curcuma xanthorrhiza and Momordica charantia have demonstrated antidiabetic potential, but comparative evaluation of their activity as DPP-4 inhibitors remains limited. Methods: Molecular docking was performed using CB-Dock2 integrated with AutoDock Vina against DPP-4 (PDB ID: 4A5S). Curcumin and xanthorrhizol from C. xanthorrhiza, and momordicin I and kuguacin J from M. charantia were evaluated. Sitagliptin was used as a positive control. Binding affinities and interactions with catalytic residues were analyzed. Pharmacokinetic and toxicity profiles were predicted using SwissADME and pkCSM. Results: All compounds demonstrated favorable binding affinities (< –7.0 kcal/mol). Kuguacin J exhibited the strongest binding (–8.7 kcal/mol), slightly exceeding sitagliptin (–8.5 kcal/mol), followed by momordicin I (–8.3 kcal/mol), curcumin (–8.2 kcal/mol), and xanthorrhizol (–7.3 kcal/mol). Key interactions involved Glu205, Glu206, Ser630, Tyr547, and Tyr662, indicating active-site occupation. ADMET analysis showed compliance with Lipinski’s rule of five and high gastrointestinal absorption for all compounds. Kuguacin J demonstrated the most favorable safety profile with no predicted Ames toxicity or hepatotoxicity. Conclusion: Kuguacin J emerges as the most promising natural DPP-4 inhibitor candidate based on combined docking and ADMET evaluation. Further experimental validation is required to confirm its therapeutic potential in T2DM management.
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