Alpha-substituted derivatives of cinnamaldehyde as tyrosinase inhibitors: inhibitory mechanism and molecular analysis.

Alpha-substituted derivatives of cinnamaldehyde (alpha-bromocinnamaldehyde, alpha-chlorocinnamaldehyde, and alpha-methylcinnamaldehyde) were used as inhibitors on mushroom tyrosinase. The result showed that three compounds can reduce both monophenolase and diphenolase activity on tyrosinase, and the inhibition was reversible. The IC50 values of alpha-bromocinnamaldehyde, alpha-chlorocinnamaldehyde, and alpha-methylcinnamaldehyde were 0.075, 0.140, and 0.440 mM on monophenolase and 0.049, 0.110, and 0.450 mM on diphenolase, respectively. The inhibition types and constants on diphenolase for these inhibitors were further studied. The molecular inhibition mechanisms of tyrosinase by the derivatives were investigated by UV-scanning study, fluorescence quenching, and molecular docking. These assays demonstrated that the derivatives could decrease the formation of o-quinones, and all derivatives were static quenchers of mushroom tyrosinase. Docking results implied that they could not form metal interactions with the copper ions of the enzyme, whereas they could interact with the amino acid residues of active site center. This research on alpha-substituted derivatives of cinnamaldehyde as tyrosinase inhibitors would lead to advances in the field of antityrosinase.