Department of Chemistry, Life Sciences and Environmental Sustainability and CIRCMSB (Consorzio Interuniversitario di Ricerca in Chimica dei Metalli nei Sistemi Biologici) Parma Unit, University of Parma, Parco Area delle Scienze 17/A, 43124 Parma, Italy.
Department of Chemistry, Life Sciences and Environmental Sustainability and CIRCMSB (Consorzio Interuniversitario di Ricerca in Chimica dei Metalli nei Sistemi Biologici) Parma Unit, University of Parma, Parco Area delle Scienze 17/A, 43124 Parma, Italy.
Food Chem. 2020 Jan 15;303:125310. doi: 10.1016/j.foodchem.2019.125310. Epub 2019 Aug 1.
Tyrosinase is a metalloenzyme involved in o-hydroxylation of monophenols and oxidation of o-diphenols to o-quinones, with formation of brown or black pigments (melanines). Tyrosinase inhibitors are of great interest in medicine and cosmetics (skin whitening compounds), but also in food and beverage industry (antibrowning agents). Here we report on the activity as mushroom tyrosinase inhibitors of a series of hydroxyphenyl thiosemicarbazones (1-5): one of them revealed an inhibitory activity stronger than kojic acid, used as reference. Enzymatic inhibition activity was confirmed by colorimetric measurements on small wheels of Fuji apples treated with the hydroxyphenyl thiosemicarbazones. The mechanism of action of compounds 1-5 was investigated by molecular modelling and by studying in solution their speciation with Cu(II) ions, the ions in the active site of the enzyme. Finally, compounds 1-5 were tested on human fibroblasts: they are not cytotoxic and they do not activate cells in a pro-inflammatory way.
酪氨酸酶是一种金属酶，参与单酚的 o-羟化和邻二酚的氧化生成 o-醌，形成棕色或黑色色素（黑色素）。酪氨酸酶抑制剂在医学和化妆品（皮肤美白化合物）中具有重要意义，在食品和饮料行业（防褐变剂）中也具有重要意义。在这里，我们报告了一系列羟苯基硫代卡巴腙（1-5）作为蘑菇酪氨酸酶抑制剂的活性：其中一种的抑制活性强于作为参考的曲酸。通过对用羟苯基硫代卡巴腙处理的富士苹果小轮进行比色测量，证实了酶的抑制活性。通过分子建模和研究化合物 1-5 在溶液中与 Cu(II)离子的形态（酶活性部位的离子），研究了化合物 1-5 的作用机制。最后，对人成纤维细胞进行了化合物 1-5 的测试：它们没有细胞毒性，也不会以促炎的方式激活细胞。
