Picolyl alkyl amines as novel tyrosinase inhibitors: influence of hydrophobicity and substitution.

Several novel picolyl alkyl amine derivatives (A-L) were synthesized, and the influence of hydrophobicity and substitution on the inhibition of mushroom tyrosinase toward both monophenolase and diphenolase activities are described. Alpha-, beta-, and gamma-picolyl amines are neither the substrates nor the inhibitors; however, the inhibition is induced by the incorporation of an alkyl chain. The inhibition was strongly dependent on the substitution on a pyridine ring, and the inhibition follows the trend of alpha-picolyl alkyl amines (A, D, G) < beta-picolyl alkyl amines (B, E, H) < gamma-picolyl alkyl amines (C, F, I). The inhibition kinetics have been investigated, and gamma-substituted derivatives were found to be a mixed type of inhibitor, whereas beta-substituted derivatives were found to exhibit uncompetitive inhibition toward the oxidation of L-DOPA.