关键词: 1,3-dipolar cycloaddition AChE Alzheimer’s disease BChE Molecular docking study Spiropyrrolidines

Mesh : Acetylcholinesterase / metabolism Animals Butyrylcholinesterase / metabolism Cholinesterase Inhibitors / chemical synthesis chemistry pharmacology Dose-Response Relationship, Drug Electrophorus Horses Ionic Liquids / chemical synthesis chemistry pharmacology Molecular Docking Simulation Molecular Structure Pyrrolidines / chemical synthesis chemistry pharmacology Structure-Activity Relationship

来  源:   DOI:10.1016/j.bioorg.2018.01.019

Abstract:
A small library of novel spiropyrrolidine heterocyclic hybrids has been prepared regioselectively in 1-butyl-3-methylimidazoliumbromide ([bmim]Br) with good to excellent yields using a [3+2] cycloaddition reaction. These synthesized compounds were evaluated as potential agents for treating Alzheimer\'s disease. Compound 4b showed the most potent activity, with an IC50 of 7.9 ± 0.25 µM against acetylcholinesterase (AChE). The inhibition mechanisms for the most active compounds on AChE and butyrylcholinesterase (BChE) receptors were elucidated using molecular docking simulations.
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