Tyrosinase Inhibition by 4-Substituted Benzaldehydes with Electron-Withdrawing Groups.

The oxidation of 4-t-butylcatechol catalyzed by mushroom tyrosinase was inhibited by 4-bromobenzaldehyde, 4-chlorobenzaldehyde, 4-fluorobenzaldehyde, 4-cyanobenzaldehyde, and 4-nitrobenzaldehyde with 50% inhibitory concentrations of 114 μM, 175 μM, 387 μM, 822 μM, and 1846 μM, respectively. The inhibition kinetics were analyzed by Dixon plots, which indicated that a series of 4-hallogenated benzaldehydes acted as partial noncompetitive inhibitors in the same manner as benzaldehyde. Although β values were decreased with an increase of the tyrosinase inhibitory activity, full inhibition could not be observed. In contrast, 4-cyanobenzaldehyde and 4-nitrobenzaldehyde acted as mixed and noncompetitive inhibitors, respectively. Full inhibition was particularly represented by 4-nitrobenzaldehyde. According to a previous report, 4-alkylbenzaldehyde and 4-alkoxybenzaldehyde with a bulky substituent acted as full inhibitors. Those results suggested that the steric factor at the 4-position triggered the alternation between partial or full tyrosinase inhibition irrespective of electronic or hydrophobic effects.