香豆素-BMT 杂合子的设计、合成及乙酰胆碱酯酶抑制活性评价。

Design, Synthesis and Bioactivity Evaluation of Coumarin-BMT Hybrids as New Acetylcholinesterase Inhibitors.

机构信息

East China Woody Fragrance and Flavor Engineering Research Center of National Forestry and Grassland Administration, College of Forestry, Jiangxi Agricultural University, Nanchang 330045, China.

Jiangxi Academy of Forestry, Nanchang 330032, China.

出版信息

Molecules. 2022 Mar 26;27(7):2142. doi: 10.3390/molecules27072142.

Coumarin possesses the aromatic group and showed plentiful activities, such as antioxidant, preventing asthma and antisepsis. In addition, coumarin derivatives usually possess good solubility, low cytotoxicity and excellent cell permeability. In our study, we synthesized the compound bridge methylene tacrine (BMT), which has the classical pharmacophore structure of Tacrine (THA). Based on the principle of active substructure splicing, BMT was used as a lead compound and synthesized coumarin-BMT hybrids by introducing coumarin to BMT. In this work, 21 novel hybrids of BMT and coumarin were synthesized and evaluated for their inhibitory activity on AChE. All obtained compounds present preferable inhibition. Compound was the most active compound, with the value of K as 49.2 nM, which was higher than Galantamine (GAL) and lower than THA. The result of molecular docking showed that the highest binding free energy was -40.43 kcal/mol for compound , which was an identical trend with the calculated K.

香豆素具有芳香基团，表现出丰富的活性，如抗氧化、预防哮喘和抗菌作用。此外，香豆素衍生物通常具有良好的溶解性、低细胞毒性和优异的细胞通透性。在我们的研究中，我们合成了化合物桥亚甲基他克林（BMT），它具有他克林（THA）的经典药效团结构。基于活性亚结构拼接原理，将 BMT 用作先导化合物，并通过将香豆素引入 BMT 来合成香豆素-BMT 杂合体。在这项工作中，合成了 21 种新型 BMT 和香豆素的杂合体，并评估了它们对 AChE 的抑制活性。所有得到的化合物都表现出较好的抑制活性。化合物是最活跃的化合物，其 K 值为 49.2 nM，高于加兰他敏（GAL），低于他克林（THA）。分子对接的结果表明，化合物的最高结合自由能为-40.43 kcal/mol，与计算出的 K 值一致。