Title:Structure-based Virtual Screening and Molecular Dynamic Simulation
Approach for the Identification of Terpenoids as Potential DPP-4 Inhibitors
Volume: 20
Issue: 4
Author(s): Ajay Aravind Pulikkottil, Amit Kumar, Kailash Jangid, Vinod Kumar and Vikas Jaitak*
Affiliation:
- Laboratory of Natural Product Chemistry, Department of Pharmaceutical Sciences and Natural Products, Central
University of Punjab, Ghudda, 151401, Bathinda, India
Keywords:
Diabetes mellitus, terpenoids, dipeptidyl peptidase-4, virtual screening, pharmacokinetic properties, molecular dynamic simulations.
Abstract:
Background: Diabetes mellitus is a metabolic disorder where insulin secretion is compromised,
leading to hyperglycemia. DPP-4 is a viable and safer target for type 2 diabetes mellitus.
Computational tools have proven to be an asset in the process of drug discovery.
Objective: In the present study, tools like structure-based virtual screening, MM/GBSA, and
pharmacokinetic parameters were used to identify natural terpenoids as potential DPP-4 inhibitors
for treating diabetes mellitus.
Methods: Structure-based virtual screening, a cumulative mode of elimination technique, was
adopted, identifying the top five potent hit compounds depending on the docking score and nonbonding
interactions.
Results: According to the docking data, the most important contributors to complex stability are
hydrogen bonding, hydrophobic interactions, and Pi-Pi stacking interactions. The dock scores
ranged from -6.492 to -5.484 kcal/mol, indicating robust ligand-protein interactions. The pharmacokinetic
characteristics of top-scoring hits (CNP0309455, CNP0196061, CNP0122006, CNP0
221869, CNP0297378) were also computed in this study, confirming their safe administration in
the human body. Also, based on the synthetic accessibility score, all top-scored hits are easily
synthesizable. Compound CNP0309455 was quite stable during molecular dynamic simulation
studies.
Conclusion: Virtual database screening yielded new leads for developing DPP-4 inhibitors. As a
result, the findings of this study can be used to design and develop natural terpenoids as DPP-4
inhibitors for the medication of diabetes mellitus.
