Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, Yunnan Provincial Center for Research & Development of Natural Products, School of Chemical Science and Technology, Yunnan University, Kunming 650091, China.
Faculty of Life Science, Southwest Forestry University, Kunming 650224, China.
Molecules. 2022 Aug 3;27(15):4950. doi: 10.3390/molecules27154950.
Rutaceae plants are known for being a rich source of coumarins. Preliminary molecular docking showed that there was no significant difference for coumarins in Clausena and Murraya, both of which had high scoring values and showed good potential inhibitory activity to the MAO-B enzyme. Overall, 32 coumarins were isolated from Murraya exotica L., including a new coumarin 5-demethoxy-10′-ethoxyexotimarin F (1). Their structures were elucidated on the basis of a comprehensive analysis of 1D and 2D NMR and HRMS spectroscopic data, and the absolute configurations were assigned via a comparison of the specific rotations and the ECD exciton coupling method. The potential of new coumarin (1) as a selective inhibitor of MAO-B was initially evaluated through molecular docking and pharmacophore studies. Compound (1) showed selectivity for the MAO-B isoenzyme and inhibitory activity in the sub-micromolar range with an IC50 value of 153.25 ± 1.58 nM (MAO-B selectivity index > 172).
芸香科植物以富含香豆素而闻名。初步分子对接表明，柠檬苦素和吴茱萸素中的香豆素没有明显差异，它们的得分值都很高，对 MAO-B 酶表现出良好的潜在抑制活性。从芸香科吴茱萸属植物九里香中分离得到 32 种香豆素，包括一种新的香豆素 5-脱甲氧基-10′-乙氧基吴茱萸素 F（1）。基于一维和二维 NMR 和高分辨质谱光谱数据的综合分析，阐明了它们的结构，并通过比较比旋光度和 ECD 激子偶合方法确定了绝对构型。通过分子对接和药效团研究，初步评价了新香豆素（1）作为 MAO-B 选择性抑制剂的潜力。化合物（1）对 MAO-B 同工酶具有选择性，在亚微摩尔范围内表现出抑制活性，IC50 值为 153.25±1.58 nM（MAO-B 选择性指数>172）。
