Tyrosinase is a multifunctional, glycosylated and copper-containing oxidase enzyme that can be found in animals, plants, and fungi. It is involved in several biological processes such as melanin biosynthesis. In this work, a series of isobenzofuran-1(3H)-ones was evaluated as tyrosinase inhibitors. It was found that compounds phthalaldehydic acid (1), 3-(2,6-dihydroxy-4-isopropylphenyl)isobenzofuran-1(3H)-one (7), and 2-(3-oxo-1,3-dihydroisobenzofuran-1-yl)-1,3-phenylene diacetate (9) were the most potent compounds inhibiting tyrosinase activity in a concentration dependent manner. Ligand-enzyme NMR studies and docking investigations allowed to map the atoms of the ligands involved in the interaction with the copper atoms present in the active site of the tyrosinase. This behaviour is similar to kojic acid, a well know tyrosinase inhibitor and used as positive control in the biological assays. The findings herein described pave the way for future rational design of new tyrosinase inhibitors.

酪氨酸酶是一种多功能的，糖基化的含铜氧化酶，可以在动物，植物和真菌中发现。它涉及多种生物过程，例如黑色素的生物合成。在这项工作中，评估了一系列异苯并呋喃-1（3 H）-ones作为酪氨酸酶抑制剂。发现化合物邻苯二酸（1），3-（2,6-二羟基-4-异丙基苯基）异苯并呋喃-1（3 H）-一（7）和2-（3-氧代-1,3-二氢异苯并呋喃）-1-基）-1,3-亚苯基二乙酸酯（9）是最有效的浓度依赖性抑制酪氨酸酶活性的化合物。配体酶NMR研究和对接研究可以绘制与酪氨酸酶活性位点中存在的铜原子相互作用的配体原子图。这种行为类似于曲酸，一种众所周知的酪氨酸酶抑制剂，在生物学分析中用作阳性对照。本文描述的发现为新型酪氨酸酶抑制剂的未来合理设计铺平了道路。