Moon Si Won, Kim Jeong Yoon, Lee Seung Hwan, Im Se Young, Lee Gihwan, Park Ki Hun
Division of Applied Life Science (BK21 Four), IALS, Gyeongsang National University, Jinju 52828, Republic of Korea.
Department of Pharmaceutical Engineering, IALS, Gyeongsang National University, Jinju 52725, Republic of Korea.
ACS Omega. 2023 Aug 23;8(35):31870-31879. doi: 10.1021/acsomega.3c03396. eCollection 2023 Sep 5.
A series of rotenoids including a new one from the seeds of were found to have significant potential as tyrosinase inhibitors. All of the isolated rotenoids () displayed inhibitory activity against tyrosinase, both as a monophenolase for the oxidation of l-tyrosine and as a diphenolase for the oxidation of l-DOPA. The three most active compounds (, , and ) showed significant monophenolase inhibition with IC values of 2.1, 1.7, and 1.2 μM, respectively. They also inhibited diphenolase function with IC values in the range of 9.5-21.5 μM. The inhibition kinetics established all compounds to be competitive inhibitors of both oxidation processes. All rotenoids formed the ·I complex effectively around their IC values with long lag times. Tyrosinase inhibition of the new rotenoid was additionally demonstrated using high-performance liquid chromatography (HPLC) analysis with -acetyl-l-tyrosine. Molecular docking disclosed that the sugar moiety of interacted with the bottom of the catalytic gorge.
人们发现，一系列鱼藤酮类化合物，包括从[植物名称]种子中分离出的一种新的鱼藤酮类化合物，具有作为酪氨酸酶抑制剂的显著潜力。所有分离得到的鱼藤酮类化合物（[化合物名称]）均表现出对酪氨酸酶的抑制活性，既作为单酚酶用于催化L-酪氨酸氧化，又作为二酚酶用于催化L-多巴氧化。三种活性最强的化合物（[化合物编号1]、[化合物编号2]和[化合物编号3]）对单酚酶的抑制作用显著，其IC50值分别为2.1、1.7和1.2 μM。它们对二酚酶功能的抑制作用，IC50值在9.5 - 21.5 μM范围内。抑制动力学表明，所有化合物对这两个氧化过程均为竞争性抑制剂。所有鱼藤酮类化合物在其IC50值附近均能有效形成·I复合物，且滞后时间较长。使用乙酰-L-酪氨酸进行高效液相色谱（HPLC）分析进一步证明了新鱼藤酮类化合物[化合物名称]对酪氨酸酶的抑制作用。分子对接结果显示，[化合物名称]的糖基部分与催化峡谷底部相互作用。
