“Click” assembly of novel dual inhibitors of AChE and MAO-B from pyridoxine derivatives for the treatment of Alzheimer’s disease

IF 1.3 3区化学 Q3 CHEMISTRY, ORGANIC

Heterocyclic Communications Pub Date : 2022-01-01 DOI:10.1515/hc-2022-0002

Zhao Jia, Huiyun Wen, Saipeng Huang, Yane Luo, Juanjuan Gao, Ruijie Wang, Kai-Ying Wan, Weiming Xue

引用次数: 1

Abstract

Abstract This study fast synthesizes numerous functionalized pyridoxines using click chemistry and assayed in vitro as inhibitors of the acetylcholinesterase (AChE), butyrylcholinesterase, and two monoamine oxidase (MAO) isoforms, MAO-A and MAO-B. Most of the obtained compounds demonstrate good AChE and selective MAO-B inhibitory activities in the micromolar range, especially one compound, called 4k5, exhibits excellent inhibitory performance against AChE (IC50 = 0.0816 ± 0.075 μM) and MAO-B (IC50 = 0.039 ± 0.003 μM). Finally, a docking study is carried out, demonstrating potential binding orientations and interactions of the compounds in terms of the AChE and MAO-B active sites.

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摘要本研究使用点击化学快速合成了许多功能化的吡哆醇，并在体外测定了其作为乙酰胆碱酯酶（AChE）、丁酰胆碱酯酶和两种单胺氧化酶（MAO）异构体MAO-A和MAO-B的抑制剂。大多数化合物在微摩尔范围内表现出良好的AChE和选择性MAO-B抑制活性，尤其是一种称为4k5的化合物对AChE表现出优异的抑制性能（IC50=0.0816±0.075 μM）和MAO-B（IC50=0.039±0.003 μM）。最后，进行了对接研究，证明了化合物在AChE和MAO-B活性位点方面的潜在结合方向和相互作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Heterocyclic Communications 化学-有机化学

CiteScore

3.80

自引率

4.30%

发文量

审稿时长

1.4 months

期刊介绍： Heterocyclic Communications (HC) is a bimonthly, peer-reviewed journal publishing preliminary communications, research articles, and reviews on significant developments in all phases of heterocyclic chemistry, including general synthesis, natural products, computational analysis, considerable biological activity and inorganic ring systems. Clear presentation of experimental and computational data is strongly emphasized. Heterocyclic chemistry is a rapidly growing field. By some estimates original research papers in heterocyclic chemistry have increased to more than 60% of the current organic chemistry literature published. This explosive growth is even greater when considering heterocyclic research published in materials science, physical, biophysical, analytical, bioorganic, pharmaceutical, medicinal and natural products journals. There is a need, therefore, for a journal dedicated explicitly to heterocyclic chemistry and the properties of heterocyclic compounds.