Cation– π and π– π stacking interactions allow selective inhibition of butyrylcholinesterase by modified quinine and cinchonidine alkaloids

Abstract

Scaffold varied quaternized quinine and cinchonidine alkaloid derivatives were evaluated for their selective butyrylcholinesterase (BChE) inhibitory potential. K i values were between 0.4–260.5 μM (non-competitive inhibition) while corresponding K ivalues to acetylcholinesterase (AChE) ranged from 7.0–400 μM exhibiting a 250-fold selectivity for BChE. Docking arrangements (GOLD, PLANT) revealed that the extended aromatic moieties and the quaternized nitrogen of the inhibitors were responsible for specific π– π stacking and π–cation interactions with the choline binding site and the peripheral anionic site of BChE’s active site.