Determination of the Inhibitory Potential of Chalcones on Myeloperoxidase Enzyme Activity: In vitro and Molecular Docking Studies

Myeloperoxidase (MPO) is a highly abundant hemoprotein in neutrophils and monocytes. It has a crucial function in immunological surveillance and the body’s defensive systems. Nevertheless, there is a strong correlation between elevated MPO activity and the development and advancement of inflammatory processes. Chalcone derivatives serve as fundamental components of pharmaceutical raw materials, which have been extensively utilized for the treatment of several ailments. In this study, it was studied the effect of some chalchones on MPO activity. Chalcones (1−6) strongly inhibited MPO with IC50s in the micromolar range of 0.05–0.828 µM. In particular, 4,4′-difluorochalcone (3) exhibited the best MPO inhibitory impact with IC50 of 0.05 µM. Additionally, molecular docking experiments were conducted to predict the binding affinities and interactions of the chalcone derivatives with the MPO active site. The docking results revealed that all tested compounds exhibited favorable binding energies, with ΔG Vina values ranging from −7.6 to −8.4 kcal/mol. Compound 3 demonstrated the strongest binding affinity (−8.4 kcal/mol), forming key hydrogen bonds with Gln91 and His95, and halogen interactions with the fluorine atoms, which may account for its enhanced inhibitory activity. These combined in vitro and in silico results suggest that chalcone derivatives hold significant potential as therapeutic candidates targeting MPO.