School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, Zhejiang, PR China.
Division of Pharmaceutical Science, King's College London, London, UK.
J Enzyme Inhib Med Chem. 2020 Dec;35(1):1562-1567. doi: 10.1080/14756366.2020.1801669.
In an attempt to synthesise new tyrosinase inhibitors, we designed and synthesised a series of chalcone-hydroxypyridinone hybrids as potential tyrosinase inhibitors adopting strategic modifications of kojic acid. All the newly synthesised compounds were characterised by NMR and mass spectrometry. Initial screening of the target compounds demonstrated that compounds , , and had relatively strong inhibitory activities against tyrosinase monophenolase, with IC values of 3.07 ± 0.85, 2.25 ± 0.8 and 2.75 ± 1.19 μM, respectively. The inhibitory activity against monophenolase was 6- to 8-fold higher than that of kojic acid. Compounds , , and also showed inhibition of diphenolase, with IC values of 17.05 ± 0.07, 11.70 ± 0.03 and 19.3 ± 0.28 μM, respectively. The inhibition kinetics of diphenolase indicates that compounds and induce reversible inhibition on tyrosinase. Finally, we found that copper coordination should be one of the important inhibitory mechanism of these compounds in tyrosinase.
为了合成新型的酪氨酸酶抑制剂，我们采用曲酸的结构改造策略，设计并合成了一系列查尔酮-羟基吡啶酮杂合体作为潜在的酪氨酸酶抑制剂。所有新合成的化合物均通过 NMR 和质谱进行了表征。对目标化合物的初步筛选表明，化合物 、 和 对酪氨酸酶单酚酶具有相对较强的抑制活性，IC 值分别为 3.07±0.85、2.25±0.8 和 2.75±1.19μM。对单酚酶的抑制活性比曲酸高 6-8 倍。化合物 、 和 对二酚酶也有抑制作用，IC 值分别为 17.05±0.07、11.70±0.03 和 19.3±0.28μM。二酚酶的抑制动力学表明，化合物 和 诱导酪氨酸酶的可逆抑制。最后，我们发现铜配位可能是这些化合物在酪氨酸酶中抑制作用的重要机制之一。
