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

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.