N-Substituted Arylidene-3-(Methylsulfonyl)-2-Oxoimidazolidine-1-Carbohydrazide as Cholinesterase Inhibitors: Design, Synthesis, and Molecular Docking Study.

The development of new enzyme inhibitors in degenerative brain diseases has gained more attention. Enzyme inhibitors play an effective role in controlling central nervous system diseases. For this purpose, a novel series of hydrazone derivatives containing imidazolidine ring aimed against Alzheimer's disease (AD), have been designed and synthesized. The acetylcholinesterase (AChE) enzyme inhibitory activity of these compounds was investigated. The structures of the compounds were determined by IR, 1 H and 13 C-NMR and mass spectroscopic methods. Inhibition studies on the cholinesterase (ChE) enzymes and β-amyloid plaque inhibition test of the compounds were performed. Based on the experimental results, compound 3j bearing dimethoxy substituent on the aromatic ring like donepezil exhibited the most AChE inhibitory activity with the IC 50 values of 0.023±0.001 μM. Owing to obtained biological activity and molecular docking study results, it is thought that the most active compound 3j may play a role in both symptomatic and palliative treatment of AD.