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

Sarfraz A Nawaz; Muhammad Ayaz; Wolfgang Brandt; Ludger A Wessjohann; Bernhard Westermann

doi:10.1016/j.bbrc.2010.12.084

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

Biochem Biophys Res Commun. 2011 Jan 28;404(4):935-40. doi: 10.1016/j.bbrc.2010.12.084. Epub 2010 Dec 23.

Authors

Sarfraz A Nawaz¹, Muhammad Ayaz, Wolfgang Brandt, Ludger A Wessjohann, Bernhard Westermann

Affiliation

¹ Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Weinberg 3, D-06120, Halle (Saale), Germany.

PMID: 21185266
DOI: 10.1016/j.bbrc.2010.12.084

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Butyrylcholinesterase / chemistry*
Catalytic Domain / drug effects
Cholinesterase Inhibitors / chemistry*
Cholinesterase Inhibitors / pharmacology
Cinchona Alkaloids / chemistry*
Cinchona Alkaloids / pharmacology
Humans
Quinine / analogs & derivatives*
Quinine / chemistry
Quinine / pharmacology

Substances

Cholinesterase Inhibitors
Cinchona Alkaloids
cinchonidine
Quinine
Butyrylcholinesterase