Title:Chemical and Molecular Aspects on Interactions of Galanthamine and Its Derivatives with Cholinesterases
VOLUME: 16 ISSUE: 3
Author(s):Hayrettin O. Gulcan, Ilkay E. Orhan and Bilge Sener
Affiliation:Department of Pharmacognosy, Faculty of Pharmacy, Gazi University, 06330 Ankara, Turkey.
Keywords:Acetylcholinesterase, butyrylcholinesterase, galanthamine, galanthamine synthesis, interaction, molecular docking.
Abstract:Dual action of galanthamine as potent cholinesterase inhibitor and nicotinic modulator has
attracted a great attention to be used in the treatment of AD. Consequently, galanthamine, a natural
alkaloid isolated from a Galanthus species (snowdrop, Amaryllidaceae), has become an attractive model
compound for synthesis of its novel derivatives to discover new drug candidates. Numerous studies have
been done to elucidate interactions between galanthamine and its different derivatives and the enzymes; acetylcholinesterase
(AChE) and butyrylcholinesterase (BChE) using in vitro and in silico experimental models. The in vitro studies
revealed that galanthamine inhibits AChE in strong, competitive, long-acting, and reversible manner as well as BChE, although
its selectivity towards AChE is much higher than BChE. The in silico studies carried out by employing molecular
docking experiments as well as molecular dynamics simulations pointed out to existence of strong interactions of galanthamine
with the active gorge of AChE, mostly of Torpedo californica (the Pasific electric ray) origin. In this review,
we evaluate the mainstays of cholinesterase inhibitory action of galanthamine and its various derivatives from the point of
view of chemical and molecular aspects.
