Effect of Organic Solvents on Acetylcholinesterase Inhibition and Enzyme Kinetics.

Q3 Psychology Central nervous system agents in medicinal chemistry Pub Date : 2023-01-01 DOI:10.2174/1871524923666230417094549

Dnyaneshwar Baswar, Awanish Mishra

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Abstract

Background: The most widespread signalling system in the brain is the cholinergic system, which plays a central role in the progress of Alzheimer's diseases (AD). Current AD treatment primarily targets the neuronal acetylcholinesterase (AChE) enzyme. The finding of AChE activity may play a vital role in optimizing assays for drug discovery of new AChE inhibiting agents. During in-vitro assay of AChE activity, the use of various organic solvents is imperative.

Objective: The present study is designed to evaluate the effect of different organic solvents on enzyme activity and enzyme kinetics.

Method: Organic solvents' AChE inhibitory potential (including enzyme kinetics: Vmax, Km and Kcat) was evaluated using substrate velocity curve by using non-linear reversion Michaelis-Menten kinetic function.

Results: DMSO was found to have the most potent AChE inhibitory effect, followed by acetonitrile and ethanol. The kinetic study revealed DMSO as a mixed inhibitory effect (competitive/noncompetitive manner), ethanol as non-competitive, and acetonitrile as a competitive inhibitor of the AChE enzyme. Methanol has shown a negligible impact on enzyme inhibition and kinetics, suggesting its suitability for the AChE assay.

Conclusion: We assume that our study results will help design the experimental protocols and support analyzing investigational outcomes while screening and biological evaluation of new molecules using methanol as solvent/cosolvent.

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有机溶剂对乙酰胆碱酯酶抑制及酶动力学的影响。

背景:大脑中最广泛的信号系统是胆碱能系统，它在阿尔茨海默病(AD)的进展中起着核心作用。目前的AD治疗主要针对神经元乙酰胆碱酯酶(AChE)。乙酰胆碱酯酶活性的发现可能在优化新的乙酰胆碱酯酶抑制剂药物发现的检测方法中发挥重要作用。在乙酰胆碱酯酶活性的体外测定中，使用各种有机溶剂是必要的。目的:研究不同有机溶剂对酶活性和酶动力学的影响。方法:采用非线性反演Michaelis-Menten动力学函数，利用底物速度曲线评价有机溶剂乙酰胆碱酯酶抑制电位(包括酶动力学:Vmax、Km和Kcat)。结果:DMSO对AChE的抑制作用最强，乙腈次之，乙醇次之。动力学研究表明DMSO是一种混合抑制效应(竞争性/非竞争性)，乙醇为非竞争性，乙腈为竞争性乙酰胆碱酯酶抑制剂。甲醇对酶抑制和动力学的影响可以忽略不计，这表明它适合AChE测定。结论:我们认为我们的研究结果将有助于设计实验方案和支持分析研究结果，同时筛选和生物学评价以甲醇为溶剂/助溶剂的新分子。

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

Central nervous system agents in medicinal chemistry Psychology-Neuropsychology and Physiological Psychology

CiteScore

2.10

自引率

0.00%

发文量

期刊介绍： Central Nervous System Agents in Medicinal Chemistry aims to cover all the latest and outstanding developments in medicinal chemistry and rational drug design for the discovery of new central nervous system agents. Containing a series of timely in-depth reviews written by leaders in the field covering a range of current topics, Central Nervous System Agents in Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments in the field.