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.