Design and synthesis of novel stilbene-hydroxypyridinone hybrids as tyrosinase inhibitors and their application in the anti-browning of freshly-cut apples

• Published in: Food chemistry 2022-08, Vol.385, p.132730-132730, Article 132730
• Main Authors: Zhu, Yu-Zhu, Chen, Kai, Chen, Yu-Lin, Zhang, Changjun, Xie, Yuan-Yuan, Hider, Robert C., Zhou, Tao
• Format: Article
• Language: English
• Subjects: Agaricales; Anti-browning; apples; catechol oxidase; color; Copper; Enzyme Inhibitors - chemistry; fluorescence; food chemistry; food industry; Hydroxypyridinone; Inhibitor; kojic acid; Malus; Molecular Docking Simulation; Monophenol Monooxygenase; Stilbene; Stilbenes; Tyrosinase
• ISSN: 0308-8146; 1873-7072
• DOI: 10.1016/j.foodchem.2022.132730

•A range of stilbene-hydroxypyridinone hybrids were prepared starting from kojic acid.•2-(3,5-Dihydroxystyryl)-1-hexyl-5-hydroxypyridin-4(1H)-one (1h) inhibited tyrosinase.•Compound 1h was a reversible and mixed-type inhibitor on diphenolase.•Copper coordination and reduction could be important inhibitory mechanism.•Compound 1h effectively retard the browning of fresh-cut apple slices. In order to develop the tyrosinase inhibitors with potential application in food industry, a series of stilbene-hydroxypyridinone hybrids were prepared. Among these compounds, 1h was found to possess the most potent tyrosinase inhibitory effect on both monophenolase and diphenolase activities, with IC50 values of 2.72 μM and 15.86 μM, respectively. The inhibitory effect of 1h on monophenolase activity was 4.6 times that of kojic acid. An inhibition kinetic assay indicated that 1h was a mixed-type and reversible inhibitor. The copper-binding and reducing ability assays, molecular docking study, intrinsic and ANS–binding fluorescence assays indicated that copper coordination and reduction is likely to be the causative mechanism for 1h-induced inhibition on tyrosinase. The results of color measurement and browning index determination indicated that treatment with 1h retarded effectively the browning of freshly-cut apples during their storage. Meanwhile, PPO and POD activities in apple slices were found to be effectively inhibited.