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 muM, 175 muM, 387 muM, 822 muM, and 1846 muM, 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 beta 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.