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

Abstract

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 6w (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 6w is a non-competitive mixed inhibitor, and this result was further confirmed by molecular docking. The fluorescence quenching mode of compound 6w is dynamic quenching, and interacts with tyrosinase by changing the amide structure of tyrosinase. Compound 6w has some anti-browning effect. Compound 6p had the strongest DPPH radical scavenging activity (IC₅₀ = 10.53 ± 0.014 μM), and compound 6w showed the best ABTS scavenging activity (IC₅₀ = 3.03 ± 0.009 μM).