Molecular Docking Study on Galantamine Derivatives as Cholinesterase Inhibitors

Abstract

A training set of 22 synthetic galantamine derivatives binding to acetylcholinesterase was docked by GOLD and the protocol was optimized in terms of scoring function, rigidity/flexibility of the binding site, presence/absence of a water molecule inside and radius of the binding site. A moderate correlation was found between the affinities of compounds expressed as pIC50 values and their docking scores. The optimized docking protocol was validated by an external test set of 11 natural galantamine derivatives and the correlation coefficient between the docking scores and the pIC50 values was 0.800. The derived relationship was used to analyze the interactions between galantamine derivatives and AChE.

Keywords: Acetylcholinesterase inhibitors, Galantamine, Molecular docking, GoldScore, Hydrogen bond, Hydrophobic interaction, π-π stacking, Cationπ interaction.