Inhibitory activity and mechanism of thiosemicarbazide derivatives on tyrosinase and their anti-browning activity in fresh apple juice

Exploring tyrosinase inhibitors has been an effective way to find promising anti-browning agents in the food industry. Therefore, a class of thiosemicarbazide derivatives (4a-4m) were synthesized and we investigated the inhibitory mechanism on tyrosinase by fluorescence quenching, copper ion chelating and UV spectra study etc. 2(2-Chlorobenzyl) hydrazine-1-carbothioamide (4f) (IC50 = 1.21 +/- 0.02 mu M) is the most active compound of all derivatives, which was defined as a mix-type inhibitor. Additionally, molecular docking and copper ions chelating studies indicated that compound 4f has the ability to inhibit the tyrosinase activity by chelating the copper ions in the active region. Furthermore, compound 4f also exhibited lower cytotoxicity, excellent aqueous solubility and outstanding anti-browning capacity in fresh apple juice. These findings indicated these derivatives could provide more possibility for developing more safer and effective anti-browning agents.