Comprehensive Computational Studies of Naturally Occurring Kuguacins as Antidiabetic Agents by Targeting Visfatin

Diabetes mellitus continues to be a major health concern for the global population. Targeting visfatin has been identified as a possible channel to manage the disease effectively. Kuguacins are triterpenoids with established antidiabetic activity. Therefore, this study examines the visfatin activating potentials of kuguacins using molecular docking, density functional theory (DFT), molecular dynamics (MD) simulation, ADMET and drug-likeness methods. The DFT studies employed B3LYP/6+3G (d, p) basis set to calculate the electronic parameters while MD simulation was performed for 100 ns. ADMET online server was used to determine their drug-likeness and pharmacokinetic properties. Kuguacin I (−11.3 kcal/mol), kuguacin F (−10.8 kcal/mol), kuguacin R (−10.8 kcal/mol) and kuguacin M (−10.2 kcal/mol) were identified as the top-ranked molecules. The quantum chemical properties of the hit molecules suggest them as suitable visfatin activators. The RMSD and RMSF plots showed that the top-ranked kuguacins were stable and suitable as visfatin activators. Also, the MMGBSA binding free energy of the ligands ranged between −43.99 kcal/mol and −34.94 kcal/mol. The ADMET and drug-likeness properties reveal the top-ranked molecules as suitable drug candidates. The findings from this study can be verified in vitro and in vivo.