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Central Nervous System Agents in Medicinal Chemistry

Author(s): Dnyaneshwar Baswar and Awanish Mishra*

DOI: 10.2174/1871524923666230417094549

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Effect of Organic Solvents on Acetylcholinesterase Inhibition and Enzyme Kinetics

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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.

Keywords: Acetylcholinesterase, organic solvents, DMSO, methanol, enzyme kinetics, Alzheimer’s disease.

Graphical Abstract

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