title: 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.
authors.affiliation: Medical University of Sofia, Faculty of Pharmacy, 2 Dunav st., 1000 Sofia, Bulgaria tel: +359 2 9236506.
authors.forename: Mariyana
authors.initials: M
authors.lastname: Atanasova
authors.affiliation: Medical University of Sofia, Faculty of Pharmacy, 2 Dunav st., 1000 Sofia, Bulgaria tel: +359 2 9236506.
authors.forename: Nikola
authors.initials: N
authors.lastname: Yordanov
authors.affiliation: Medical University of Sofia, Faculty of Pharmacy, 2 Dunav st., 1000 Sofia, Bulgaria tel: +359 2 9236506.
authors.forename: Ivan
authors.initials: I
authors.lastname: Dimitrov
authors.affiliation: Institute of Biodiversity and Ecosystem Research, 23 Acad. G Bonchev str, 1113 Sofia, Bulgaria.
authors.forename: Strahil
authors.initials: S
authors.lastname: Berkov
authors.affiliation: Medical University of Sofia, Faculty of Pharmacy, 2 Dunav st., 1000 Sofia, Bulgaria tel: +359 2 9236506. idoytchinova@pharmfac.net.
authors.forename: Irini
authors.initials: I
authors.lastname: Doytchinova
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry; D002800:Cholinesterase Inhibitors / Q000737:chemistry*; D058851:GPI-Linked Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry; D005702:Galantamine / Q000031:analogs & derivatives / Q000737:chemistry; D006801:Humans; D062105:Molecular Docking Simulation
chemical_list: D002800:Cholinesterase Inhibitors; D058851:GPI-Linked Proteins; D005702:Galantamine; C548244:ACHE protein, human; D000110:Acetylcholinesterase
keywords: Acetylcholinesterase inhibitors, Galantamine, Molecular docking, GoldScore, Hydrogen bond, Hydrophobic interaction, π-π stacking, Cationπ interaction