Design, synthesis and anti-Alzheimer's disease activity study of xanthone derivatives based on multi-target strategy.,Bioorganic & Medicinal Chemistry Letters

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Design, synthesis and anti-Alzheimer's disease activity study of xanthone derivatives based on multi-target strategy.
Bioorganic & Medicinal Chemistry Letters ( IF 2.5 ) Pub Date : 2019-12-23 , DOI: 10.1016/j.bmcl.2019.126927
Xiaodi Kou ₁ , Lulu Song ₁ , Yunhua Wang ₂ , Qiao Yu ₁ , Hui Ju ₁ , Aihong Yang ₁ , Rui Shen ₁

Affiliation

A series of xanthone derivatives were designed, synthesized and evaluated as multifunctional ligands against Alzheimer's disease (AD). In vitro studies showed all xanthone derivatives had good metal chelating property and exhibited selective inhibitory activity against Acetylcholinesterase (AChE). In particular, compound 2a showed the highest inhibitory activity against AChE, and the IC50 value was (0.328 ± 0.001) μM, which was comparable to tacrine. Kinetic analysis and molecular docking studies indicated that these derivatives targeted both the catalytically active site (CAS) and the peripheral anion site (PAS) of AChE. Moreover, all derivatives showed higher anti-oxidative activity than vitamin C. Furthermore, copper complex had higher anti-AChE activity and antioxidant activity. Thus, these xanthone derivatives are potential multi-targeted-directed ligands for further development for the treatment of AD.

中文翻译：

基于多目标策略的of吨酮衍生物的设计，合成和抗阿尔茨海默氏病活性研究。

设计，合成和评估了一系列的黄酮衍生物，作为对抗阿尔茨海默氏病（AD）的多功能配体。体外研究表明，所有黄嘌呤衍生物均具有良好的金属螯合性能，并表现出对乙酰胆碱酯酶（AChE）的选择性抑制活性。尤其是，化合物2a对AChE的抑制活性最高，IC50值为（0.328±0.001）μM，与他克林相当。动力学分析和分子对接研究表明，这些衍生物既靶向AChE的催化活性位点（CAS），又靶向外周阴离子位点（PAS）。此外，所有衍生物均显示出比维生素C高的抗氧化活性。此外，铜络合物具有较高的抗AChE活性和抗氧化活性。因此，

更新日期：2019-12-23

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