Novel kojic acid-1,2,4-triazine hybrids as anti-tyrosinase agents: Synthesis, biological evaluation, mode of action, and anti-browning studies

A class of new kojic acid hybrids (7a-7o) bearing a 1,2,4-triazine moiety were prepared, and their inhibitory activities and mechanism on tyrosinase were investigated. All derivatives showed good to excellent anti-tyrosinase activity with IC50 values ranging from 0.34 +/- 0.06 mu M to 8.44 +/- 0.73 mu M. In kinetic study, com-pound 7m was a mixed-type inhibitor with Ki and Kis of 0.73 and 1.27 mu M, respectively. The interaction mechanism toward tyrosinase of compound 7m was further elaborated in combination with molecular docking and various spectral techniques. The results showed that compound 7m could change the secondary structure of tyrosinase to reduce its catalytic activity. Anti-browning assays demonstrated that 7m inhibited the browning of bananas effectively during storage. What's more, 7m was found to have low cytotoxicity in vitro. In conclusion, compound 7m has the potential to be applied as an anti-browning agent.