Acetylcholinesterase Activity Monitoring and Natural Anti-neurological Disease Drug Screening via Rational Design of Deep Eutectic Solvents and CeO₂-Co(OH)₂ Nanosheets

Abstract

The activity monitoring of acetylcholinesterase (AChE) and the screening of its inhibitors are critical for the diagnosis and therapy of neurological diseases. Herein, CeO2-Co­(OH)2 nanosheets were synthesized for the first time in a newly designed deep eutectic solvent (DES) composed of l-proline and Ce­(NO3)3·6H2O, and a colorimetric assay was developed for quantitative detection of AChE and anti-neurological disease drug screening. Impressively, CeO2-Co­(OH)2 composites prepared in DESs have more prominent oxidase-like activity than Co­(OH)2, CeO2, and CeO2-Co­(OH)2 produced in aqueous solution. The mechanism study shows that the oxygen vacancies of CeO2-Co­(OH)2 play a vital role in oxidase-like catalysis. Based on their excellent oxidase-like activity, the CeO2-Co­(OH)2 nanosheets have been successfully applied for highly sensitive and selective detection of AChE with a linear range of 0.2–20 mU/mL. This strategy can also be used for inhibitor screening. The sensor displays an excellent linear response in the range of 0.001–2 μg/mL toward an irreversible inhibitor (paraoxon-ethyl). Moreover, five alkaloids, namely, berberine hydrochloride, caffeine, camptothecin, matrine, and evodiamine, were screened by using neostigmine bromide as a control; berberine hydrochloride exhibited a good inhibitory effect on AChE with an IC50 of 0.94 μM, while the other four had no obvious inhibitory effect. The mechanism of the different effects of alkaloids on inhibiting acetylcholinesterase activity was explored via molecular docking and kinetic simulation.

Screening of acetylcholinesterase inhibitory and antioxidant active compounds from Terminalia chebula fruits by spectrum‐effect relationship and liquid chromatography‒mass spectrometry analysis

“…The longer the arrow is, the greater the contribution of a variable to PC. Therefore, 12 common peaks (1,2,3,4,5,6,8,9,11,12,14,15) were used for the subsequent correlation analysis between chemical components and efficacy.…”

“…Traditional Chinese medicines (TCMs) or plant-derived compounds have shown multitargeting ability in treating AD. It has been reported that Zanthoxylum nitidum [4], Scutellaria baicalensis [5], and Coptis chinensis [6] exhibit significant inhibitory effects on acetylcholinesterase (AChE) and strong antioxidant activities, becoming great potential protectors of the cholinergic system. Therefore, screening active compounds from TCMs is an important avenue to develop new drugs for multitarget therapy for AD.…”

“…Several methods have been used to screen active compounds, such as affinity ultrafiltration, biological sensors and nanoenzymes, electrochemical analysis, and immobilization of target molecules [6,8,[10][11][12][13][14]. However, there are some shortcomings, such as false-positive effects, preparation of carrier materials, and the need for expensive equipment, thus limiting their applications.…”

An aptamer and flower-shaped AuPtRh nanoenzyme-based colorimetric biosensor for the detection of profenofos

“…HPR can catalyze the oxidation reaction between H 2 O 2 and the substrate. [18][19][20] The common substrates are 3,3′,5,5′-tetramethylbenzidine (TMB), O-phenylenediamine (OPD) and 2,2′-acridine bis(3-ethylbenzothiazolin-6-sulfonic acid) (ABTS). After oxidation, the solution color would become blue, yellow and green, respectively.…”

MnO2/DNAzyme-mediated ratiometric fluorescence assay of acetylcholinesterase

“…6 AChE has become a vital biomarker and drug target in clinical diagnosis and detoxification therapy. Thus, the accurate assaying of AChE activity is highly significant from the clinical point of view, and various analytical methods have been established for this purpose, including Ellman's colorimetric, 7,8 chemiluminescent 9,10 and electrochemical approaches. 11,12 The treatment of real biological samples, however, is always highly challenging due to the interference from biomolecules and the instability of reagents.…”