High Selectivity of Dipeptidyl Peptidase 4 Receptor Towards 13 Aromatic Compounds in Cinnamomi ramulus Extract: Molecular Docking and Molecular Dynamics †

Abstract

Dipeptidyl peptidase 4 (DPP4) plays a pivotal role in the treatment of type 2 diabetes as an important glucose-regulating enzyme. We evaluated the molecular interactions between 13 major aromatic compounds from Cinnamomi ramulus and DPP4 enzyme through molecular docking simulation and molecular dynamics. The results showed that the studied compounds exhibited a wide range of docking energies with DPP4, in which benzyl benzoate was the most promising compound with a docking energy of −7.4 kcal/mol, which was comparable with that of saxagliptin and alogliptin. Detailed analysis revealed that hydrophobic interactions (three–eight interactions/complex) and hydrogen bonds (three–five bonds in some complexes) played major roles in stabilizing the complexes. Molecular dynamics simulation results demonstrated ligand selectivity for the DPP4 receptor, with only four out of 13 tested compounds stabilizing at the interaction site. Evaluation results of the method using Lipinski’s rule showed that all compounds met four–five criteria for drug-likeness, indicating potential for drug development. These results provide the first scientific evidence of the potential molecular mechanism of cinnamon bark in the treatment of type 2 diabetes through DPP4 inhibition.