Benzonitriles as tyrosinase inhibitors with hyperbolic inhibition manner

As a novel mushroom tyrosinase inhibitor, 4-methoxybenzonitrile (anisnitrile) was identified (IC₅₀ = 111.1 μM) with hyperbolic inhibition manner. The calculated αK_i (166.3 μM) was larger than K_i (66.5 μM) by Dixon plots, indicating that this nitrile acts as a competitive-noncompetitive mixed type inhibitor. Similarly, 4-isopropylbenzonitrile (cuminnitrile) partially inhibited the oxidation catalyzed by tyrosinase (IC₅₀ = 121.5 μM, K_i = 88.8 μM, and αK_i = 239.8 μM). Nine other benzonitriles also exhibited partial tyrosinase-inhibitory activity. In particular, 4-methylbenzonitrile (IC₅₀ = 79.9 μM) is considered to be the most potent among the tested benzonitriles. Benzonitriles barely caused intermolecular amidine formation under physiologic conditions. Furthermore, they possibly coordinate copper at the active site of tyrosinase. Hence, benzonitriles exhibit different inhibition characteristics as compared with that exhibited by benzaldehydes.