Development of novel pyrazole-1,2,4-triazole derivatives as tyrosinase inhibitors: Design, preparation, mechanism of action and anti-browning application

Tyrosinase (Polyphenol oxidase), a key enzyme in enzymatic browning, is an attractive target for developing new anti-browning agents in the food industry. In this work, twenty pyrazole-1,2,4-triazole derivatives ( 3a-3n, 4a-4f) were synthesized and tested in vitro, most of compounds showed potent anti-tyrosinase activity. Of these, 3c (IC 50  = 1.02 ± 0.08 μM) was found to be 14 folds stronger than kojic acid (IC 50  = 14.74 ± 1.23 μM) and behaved as a mixed type inhibitor. Besides, the disappeared peak of dopaquinone in the HPLC assay intuitively validated the inhibitory effect of 3c . Copper ions chelating, fluorescence quenching and molecular docking assays showed that coordination with copper is the key to play a role. Furthermore, 3c exhibited excellent anti-browning ability for the Rosa roxburghii Tratt, the non-enzymatic browning experiment showed that 3c could prevent browning in non-enzymatic ways. It is suggested that these derivatives could serve as the leading compounds to find more efficient anti-browning agents in the future.