Design, synthesis and anti-browning mechanistic study of Trolox derivatives with dual antioxidant and tyrosinase inhibitory properties.

Abstract

To obtain molecules with dual activities of antioxidant effect and tyrosinase inhibition, a new series of Trolox derivatives (5a-5g) were constructed by incorporating thiosemicarbazone moieties into Trolox based on the molecular hybridization principle. In vitro antioxidant and tyrosinase inhibition assays showed that compound 5a exhibited better antioxidant activity than Vitamin C, and its tyrosinase inhibitory activity was 11 times that of kojic acid. Structure-activity relationship analysis revealed that Trolox and thiosemicarbazone moiety in 5a were crucial for its antioxidant and tyrosinase inhibitory activities. Kinetic assays identified 5a as a reversible mixed-type inhibitor. Furthermore, the mechanism underlying tyrosinase inhibition was elucidated using copper ion chelation, fluorescence quenching, CD spectroscopy, and molecular docking. The mechanism study indicated that 5a interacted with tyrosinase through copper chelation, hydrogen bonding, and hydrophobic interactions, thereby reducing the enzyme activity. Furthermore, 5a could prevent browning in fresh-cut potatoes through its antioxidant and anti-tyrosinase activities.