Synthesis, anti-browning effect and mechanism research of kojic acid-coumarin derivatives as anti-tyrosinase inhibitors

• Published in: Food Chemistry: X Vol. 21; p. 101128
• Main Authors: He, Min, Zhang, Jinfeng, Li, Na, Chen, Lu, He, Yan, Peng, Zhiyun, Wang, Guangcheng
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 30.03.2024; Elsevier
• Subjects: Anti-browning; Coumarin; Kojic acid; TYR inhibitors; Anti-browning; TYR inhibitors; Coumarin; Kojic acid
• ISSN: 2590-1575; 2590-1575
• DOI: 10.1016/j.fochx.2024.101128

•Thirteen kojic acid-coumarin hybrids (6a-6 m) were designed and synthesized.•All derivatives showed better anti-tyrosinase activity than kojic acid.•Compound 6f can alter the secondary structure of tyrosinase.•Compound 6f significantly inhibited the browning of fresh lotus root slices.•Compound 6f had low cytotoxic activity. Thirteen kojic acid-coumarin derivatives were synthesized using the principle of molecular hybridization, and their structures were characterized by 1H NMR, 13C NMR, and HRMS. In vitro enzyme inhibition experiments showed that all newly synthesized derivatives have excellent inhibition of tyrosinase (TYR) activity. As a mixed inhibitor, compound 6f has the strongest activity, with an IC50 value of 0.88 ± 0.10 µM. Multispectral experiments have confirmed that the mode of action of compound 6f on TYR was static quenching. In addition, compound 6f formed a new complex with TYR, which increased the hydrophobicity of the enzyme microenvironment, reduced the content of the α-helix in the enzyme, and changed the secondary structure. The experimental results showed that compound 6f effectively inhibited the browning of lotus root slices and had low cytotoxicity. Therefore, compound 6f is believed to have great development potential as a TYR inhibitor in the food industry.