Kim Donghyun, Park Jiyeoun, Kim Jinhee, Han Cheolkyu, Yoon Jeonghyeok, Kim Namdoo, Seo Jinho, Lee Choonghwan
Korea Research Institute of Bioscience and Biotechnology, Yuseong, Daejeon, 305-333, Korea.
J Agric Food Chem. 2006 Feb 8;54(3):935-41. doi: 10.1021/jf0521855.
Flavonoids, a group of naturally occurring antioxidants and metal chelators, can be used as tyrosinase inhibitors due to their formation of copper-flavonoid complexes. Thus, to investigate the underlying inhibition mechanism, a large group of flavonoids from several major flavones and flavonols were tested using fluorescence quenching spectroscopy. In addition, large differences in the tyrosinase inhibitory activities and chelating capacities according to the location of the hydroxyl group(s) in combination with the A and B rings in the flavonoids were confirmed. Accordingly, the major conclusions from this work are as follows: (i) The tyrosinase inhibitory activity is not only dependent on the number of hydroxyl groups in the flavonoids, (ii) the enzyme is primarily quenched by the hydroxyl group(s) of A and B rings on the ether side of the flavonoids, and (iii) the tyrosinase inhibitory activity of 7,8,3',4'-tetrahydroxyflavone is supported by a virtual model of docking with the mushroom tyrosinase, which depicts the quenching of the enzyme. The results also demonstrated that the dihydroxy substitutions in the A and B rings are crucial for Cu2+-chelate formation, thereby influencing the tyrosinase inhibitory activity.
黄酮类化合物是一类天然存在的抗氧化剂和金属螯合剂，由于它们能形成铜 - 黄酮类化合物复合物，因此可作为酪氨酸酶抑制剂。因此，为了研究其潜在的抑制机制，使用荧光猝灭光谱法对来自几种主要黄酮和黄酮醇的一大类黄酮类化合物进行了测试。此外，还证实了根据黄酮类化合物中A环和B环上羟基位置的不同，其酪氨酸酶抑制活性和螯合能力存在很大差异。据此，这项工作的主要结论如下：（i）酪氨酸酶抑制活性不仅取决于黄酮类化合物中羟基的数量，（ii）该酶主要被黄酮类化合物醚侧A环和B环上的羟基猝灭，（iii）7,8,3',4'-四羟基黄酮与蘑菇酪氨酸酶的对接虚拟模型支持了其对酪氨酸酶的抑制活性，该模型描绘了酶的猝灭。结果还表明，A环和B环上的二羟基取代对于Cu2+螯合物的形成至关重要，从而影响酪氨酸酶抑制活性。
