Design, Synthesis, and Evaluation of Bioactivities of Chalcone Derivatives Containing Indole and Benzothiophene Moieties for Monoamine Oxidase and Cholinesterase Inhibition

doi:10.6023/cjoc202412042

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基于包含吲哚环、苯并噻吩环的MAO和ChE抑制活性的查尔酮衍生物设计、合成及生物活性研究

汤敏^†, 张斌^†, 王秋实, 方超华, 胡立威, 关丽萍^*

浙江海洋大学食品与药学学院浙江舟山 316022

收稿日期:2025-01-27 修回日期:2025-02-27
作者简介:^†这些作者对这项工作作出了同样的贡献
基金资助:
国家自然科学基金（No. 21964017）、福建省创新药物靶点研究重点实验室项目（No. FJ-YW-2023KF04）资助

Design, Synthesis, and Evaluation of Bioactivities of Chalcone Derivatives Containing Indole and Benzothiophene Moieties for Monoamine Oxidase and Cholinesterase Inhibition

Tang Min^†, Zhang Bin^†, Wang Qiu-shi, Fang Chao-hua, Hu Li-wei, Guan Li-ping^*

Food and Pharmacy College, Zhejiang Ocean University, Zhejiang, Zhoushan 316022, P. R. China

Received:2025-01-27 Revised:2025-02-27
Contact: * E-mail: glp730@zjou.edu.cn

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Abstract

In this thesis, 31 chalcone derivatives (1a-1ae) containing indole and benzothiophene rings were designed and synthesized. Their biological activities in inhibiting cholinesterase (ChE) and monoamine oxidase (MAO) were subsequently investigated. The cholinesterase test results indicated that all compounds exhibited minimal inhibitory effects on acetylcholinesterase (AChE). However, certain compounds demonstrated notable inhibitory effects on butyrylcholinesterase (BuChE), with compounds 1a and 1h showing the strongest inhibition rates of 85.55% and 76.43%, respectively.The findings from the monoamine oxidase experiments indicated that some of the compounds exhibited specific inhibitory effects on monoamine oxidase. Compounds exhibiting inhibitory activity exceeding 50%—specifically, 1c, 1f, 1g, 1v, and 1aa—were further evaluated for their effects on MAO-A and MAO-B enzymatic activities. It was observed that compounds 1c, 1f, and 1aa displayed comparatively superior inhibitory activity against both MAO-A and MAO-B.Results from cytotoxicity assays indicated that the compounds demonstrating enhanced inhibitory activity did not exhibit cytotoxic effects on L929 cells. Additionally, the results of molecular docking of compounds 1a, 1c and 1f showed significant interaction between compounds 1a and 1f with BuChE and between compounds 1c and 1f with MAO-A and MAO-B.

Key words: Indole chalcone, benzothiophene chalcone, cholinesterase, monoamine oxidase, cytotoxicity, molecular docking

Cite this article

Tang Min, Zhang Bin, Wang Qiu-shi, Fang Chao-hua, Hu Li-wei, Guan Li-ping. Design, Synthesis, and Evaluation of Bioactivities of Chalcone Derivatives Containing Indole and Benzothiophene Moieties for Monoamine Oxidase and Cholinesterase Inhibition[J]. Chinese Journal of Organic Chemistry, doi: 10.6023/cjoc202412042.

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基于包含吲哚环、苯并噻吩环的MAO和ChE抑制活性的查尔酮衍生物设计、合成及生物活性研究

Design, Synthesis, and Evaluation of Bioactivities of Chalcone Derivatives Containing Indole and Benzothiophene Moieties for Monoamine Oxidase and Cholinesterase Inhibition

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