title: 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 0.4-260.5μM (non-competitive inhibition) while corresponding K(i)values to acetylcholinesterase (AChE) ranged from 7.0-400μM 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.
authors.affiliation: Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Weinberg 3, D-06120, Halle (Saale), Germany.
authors.forename: Sarfraz A
authors.initials: SA
authors.lastname: Nawaz
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ayaz
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Brandt
authors.forename: Ludger A
authors.initials: LA
authors.lastname: Wessjohann
authors.forename: Bernhard
authors.initials: B
authors.lastname: Westermann
mesh_terms: D002091:Butyrylcholinesterase / Q000737:chemistry*; D020134:Catalytic Domain / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D002930:Cinchona Alkaloids / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D011803:Quinine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D002800:Cholinesterase Inhibitors; D002930:Cinchona Alkaloids; C041622:cinchonidine; D011803:Quinine; D002091:Butyrylcholinesterase