Ionic liquid-enabled synthesis, cholinesterase inhibitory activity, and molecular docking study of highly functionalized tetrasubstituted pyrrolidines

New tetrasubstituted pyrrolidine heterocyclic hybrids have been achieved regioselectively in [bmim]Br and were evaluated as potential agents for Alzheimer’s disease. The mechanism of inhibition of the most active compounds on AChE and BChE receptors were disclosed using molecular docking simulation. [Display omitted] •Heterocyclic hybrids 4a-j were synthesized in an ionic liquid, 1-butyl-3-methylimidazolium bromide ([bmim]Br).•The structure of 4a-j was confirmed from FT-IR, 1D & 2D NMR spectroscopic studies.•The compounds were evaluated as potential agents for Alzheimer’s disease.•Molecular docking simulation was performed for the most active compounds on AChE and BChE receptors. 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.