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

The activity monitoring of acetylcholinesterase(AChE) and the screening of its inhibitors are critical for thediagnosis and therapy of neurological diseases. Herein, CeO2-Co(OH)2nanosheets were synthesized for thefirst time in a newlydesigned deep eutectic solvent (DES) composed ofL-proline andCe(NO3)3middot6H2O, and a colorimetric assay was developed forquantitative detection of AChE and anti-neurological disease drugscreening. Impressively, CeO2-Co(OH)2composites prepared inDESs have more prominent oxidase-like activity than Co(OH)2,CeO2, and CeO2-Co(OH)2produced in aqueous solution. Themechanism study shows that the oxygen vacancies of CeO2-Co(OH)2play a vital role in oxidase-like catalysis. Based on theirexcellent oxidase-like activity, the CeO2-Co(OH)2nanosheets havebeen successfully applied for highly sensitive and selective detection of AChE with a linear range of 0.2-20 mU/mL. This strategycan also be used for inhibitor screening. The sensor displays an excellent linear response in the range of 0.001-2 mu g/mL toward anirreversible 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 inhibitoryeffect on AChE with an IC50of 0.94 mu M, while the other four had no obvious inhibitory effect. The mechanism of the differenteffects of alkaloids on inhibiting acetylcholinesterase activity was explored via molecular docking and kinetic simulation.