Hydroxyphenyl thiosemicarbazones as inhibitors of mushroom tyrosinase and antibrowning agents

Abstract

Tyrosinase is a metalloenzyme involved in o-hydroxylation of monophenols and oxidation of o-diphenols to o-quinones, with formation of brown or black pigments (melanines). Tyrosinase inhibitors are of great interest in medicine and cosmetics (skin whitening compounds), but also in food and beverage industry (antibrowning agents). Here we report on the activity as mushroom tyrosinase inhibitors of a series of hydroxyphenyl thiosemicarbazones (1-5): one of them revealed an inhibitory activity stronger than kojic acid, used as reference. Enzymatic inhibition activity was confirmed by colorimetric measurements on small wheels of Fuji apples treated with the hydroxyphenyl thiosemicarbazones. The mechanism of action of compounds 1-5 was investigated by molecular modelling and by studying in solution their speciation with Cu(II) ions, the ions in the active site of the enzyme. Finally, compounds 1-5 were tested on human fibroblasts: they are not cytotoxic and they do not activate cells in a pro-inflammatory way.

Keywords: Antibrowning activity; Equilibrium constant; Food browning; Kojic acid; Thiosemicarbazone; Tyrosinase inhibitor.