Study on the synthesis and biological activity of kojic acid triazol thiosemicarbazide Schiff base derivatives

A series of kojic acid triazol thiosemicarbazide Schiff base derivatives were designed and synthesised. Evaluation on the inhibition of tyrosinase activity showed that these compounds possessed potent inhibit tyrosinase activity, and the compound <b>6w</b> (IC₅₀ = 0.94 μM) exhibited the best inhibitory effect. Preliminary structure-activity relationships indicate that steric hindrance, halogen atom radius, and electron donating ability of functional groups have some impact on the inhibition of tyrosinase activity. Inhibition mechanism showed that compound <b>6w</b> is a non-competitive mixed inhibitor, and this result was further confirmed by molecular docking. The fluorescence quenching mode of compound <b>6w</b> is dynamic quenching, and interacts with tyrosinase by changing the amide structure of tyrosinase. Compound <b>6w</b> has some anti-browning effect. Compound <b>6p</b> had the strongest DPPH radical scavenging activity (IC₅₀ = 10.53 ± 0.014 μM), and compound <b>6w</b> showed the best ABTS scavenging activity (IC₅₀ = 3.03 ± 0.009 μM).