Synthesis and biological evaluation of new kojic acid-1,3,4-oxadiazole hybrids as tyrosinase inhibitors and their application in the anti-browning of fresh-cut mushrooms

Abstract

In the food industry, inhibition of tyrosinase activity is considered as one of the main means to prevent browning. Therefore, fourteen kojic acid-1,3,4-oxadiazole hybrids (5a-5n) were prepared and tested for their tyrosinase inhibitory effects. Among them, 5f (IC₅₀ = 5.32 ± 0.58 μM) has the best anti-tyrosinase activity and was 9 times higher than that of kojic acid (IC₅₀ = 49.77 ± 1.19 μM). Additionally, the inhibitory mechanism was studied by copper-chelating assay, ultraviolet spectrophotometry, fluorescence quenching, molecular docking, etc. The results had shown that 5f could not only bind to the copper ion in the active region of tyrosinase but also change the secondary structure of tyrosinase. Combined with the outstanding anti-browning effect and low cytotoxicity of 5f, it is concluded that these title derivatives could be used as the leading molecules in the development of new anti-browning agents.

Keywords: 13 4-Oxadiazole; Anti-browning agent; Anti-tyrosinase.