A type of phenolic compound, hydroxyacetophenone: tyrosinase inhibition mechanism evaluation by application of biochemical assay and computational molecular dynamics

Screening and developing tyrosinase inhibitors with novel structures are notable to receive attention in the field of skin pigmentation research due to their application in hyperpigmentation control. Hydroxyacetophenone is a natural antioxidant found in the <i>Picea abies</i> (Norwegian spruce) needles and is widely used in the cosmetic industry as an antioxidant ingredient. In this study, integrations of virtual molecular dynamics (MD) simulations and biochemical inhibition kinetics were conducted to validate the inhibitory function of hydroxyacetophenone on tyrosinase. Docking and 100 ns MD simulations revealed that hydroxyacetophenone docks onto the active site of tyrosinase, and the eight key binding residues (HIS61, CYS83, HIS85, PHE90, HIS259, ASN260, HIS263, and VAL283) were identified through distance-time profile analysis. Subsequently, serial comparisons of inhibition kinetics including a spectrometry study were conducted to validate the simulation results. Hydroxyacetophenone displayed a typical reversible and competitive type of inhibition. Measurements of the fluorescence spectrum showed hydroxyacetophenone modulated the hydrophobic condition of active site pocket in tyrosinase. Taken together, one phenolic hydroxyl group of hydroxyacetophenone exerts a hub function in tyrosinase catalytic retardation <i>via</i> ligand binding. This study illustrates the new utility of hydroxyacetophenone function in the whitening agent-related industry as a tyrosinase inhibitor.