一类新型苯并噻吩查尔酮类化合物作为乙酰胆碱酯酶抑制剂的研究：合成、生物评价、分子对接和 ADME 研究。

A New Class of Benzo[]thiophene-chalcones as Cholinesterase Inhibitors: Synthesis, Biological Evaluation, Molecular Docking and ADME Studies.

机构信息

Department of Live and Environmental Sciences, University of Cagliari, Cittadella Universitaria, SS 554, Km 4.5, 09042 Monserrato, Italy.

Departamento de Química Orgánica, Facultad de Farmacia, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain.

出版信息

Molecules. 2024 Aug 7;29(16):3748. doi: 10.3390/molecules29163748.

DOI:10.3390/molecules29163748

PMID:39202830

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11356821/

Abstract

In this study, heterocyclic compounds containing a benzothiophene scaffold were designed and synthetized, and their inhibitory activity against cholinesterases (ChE) and the viability of SH-SY5Y cells have been evaluated. Benzothiophenes - and benzothiophene-chalcone hybrids - were tested against both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), revealing interesting structure-activity relationships. In general, benzothiophene-chalcone hybrids from series proved to be better inhibitors of both enzymes, with compound being the best AChE inhibitor (IC = 62.10 μM) and compound being the best BChE inhibitor (IC = 24.35 μM), the last one having an IC similar to that of galantamine (IC = 28.08 μM), the reference compound. The in silico ADME profile of the compounds was also studied. Molecular docking calculations were carried out to analyze the best binding scores and to elucidate enzyme-inhibitors' interactions.

摘要

在这项研究中，设计并合成了含有苯并噻吩骨架的杂环化合物，并评估了它们对胆碱酯酶（ChE）的抑制活性和 SH-SY5Y 细胞的活力。苯并噻吩和苯并噻吩-查尔酮杂合体针对乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BChE）进行了测试，揭示了有趣的构效关系。一般来说，系列中的苯并噻吩-查尔酮杂合体对两种酶都是更好的抑制剂，其中化合物是最好的 AChE 抑制剂（IC = 62.10 μM），化合物是最好的 BChE 抑制剂（IC = 24.35 μM），后者的 IC 与加兰他敏（IC = 28.08 μM）相似，加兰他敏是参考化合物。还研究了化合物的计算 ADME 概况。进行了分子对接计算以分析最佳结合分数并阐明酶-抑制剂的相互作用。