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 mu M (non-competitive inhibition) while corresponding K(i)values to acetylcholinesterase (AChE) ranged from 7.0-400 mu M 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 pi-pi stacking and pi-cation interactions with the choline binding site and the peripheral anionic site of BChE's active site. (C) 2010 Elsevier Inc. All rights reserved.