Evaluation of Terpenoids as Dipeptidyl Peptidase 4 Lead Molecules: Molecular Docking and Dynamics Simulation Study

About 966 billion US dollars have been spent globally treating and managing diabetic patients. Notwithstanding individuals' substantial access to the required primary medical services and essential medicines, it is tempting to get momentum in identifying new chemical entities, biologics, or small molecules as drug candidates that are prophylactically and therapeutically effective against lifestyle-based maladies, thereby backing the overall health mission of Sustainable Development Goals. Towards this context, the study aims to screen natural inhibitor(s) targeting dipeptidyl peptidase 4 using hybrid approaches of bioinformatics and medicinal chemistry. Data set of 513 ligands of terpenoids in nature was retrieved from the naturally occurring plant-based anticancerous compound-activity-target database (NPACT) and performed docking studies. Sitagliptin depicted substantial binding affinity among reference drugs with dipeptidyl peptidase 4 (DPP IV) (binding energy: -8.63 kcal/mol, Inhibition constant: 163.65 μM). Among all terpenoids, Asiatic acid (ΔG: -9.95 kcal/mol, 85.23 μM), Aucubin (-9.86 kcal/mol, 98.98 μM), Ailanquassin A (-9.25 kcal/mol, 156.23 μM), and 6-α-hydroxyneopulchellin (-9.18 kcal/mol, 189.76 μM) depicted strong binding affinities with DPP IV compared to Sitagliptin. Based on the MD simulation findings, Asiatic acid and Aucubin were better lead molecules than Sitagliptin. However, holistic wet-lab validations are required before manifesting their therapeutic implications against diabetes.