title: In Vitro Inhibitory Effects of 8-O-Demethylmaritidine and Undulatine on Acetylcholinesterase and Their Predicted Penetration across the Blood-Brain Barrier.
abstract: Alzheimer's disease is the most common cause of dementia. Currently, acetylcholinesterase (AChE) inhibition is the most widely used therapeutic treatment. A large number of naturally occurring compounds have been found to inhibit AChE. In this report the mechanism of AChE inhibition of two Amaryllidaceae alkaloids, 8-O-demethylmaritidine (1) and undulatine (2), and their possible penetration across the blood-brain barrier have been studied. Both compounds act via a mixed inhibition mechanism. Based on the parallel artificial permeation assay (PAMPA) for the prediction of blood-brain barrier (BBB) penetration, only 2 should be able to cross the BBB by passive permeation.
authors.affiliation: †ADINACO Research Group, Department of Pharmaceutical Botany and Ecology, Faculty of Pharmacy, Charles University, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic.
authors.forename: Lucie
authors.initials: L
authors.lastname: Cahlíková
authors.affiliation: ‡Centro de Investigaciones Biológicas, Avenida Ramiro de Maeztu, 9, 28040 Madrid, Spain.
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Pérez
authors.affiliation: §Department of Biological and Biochemical Sciences, Faculty of Chemical Technology, University of Pardubice, Studentská 95, 532 10 Pardubice, Czech Republic.
authors.forename: Šárka
authors.initials: Š
authors.lastname: Štěpánková
authors.affiliation: †ADINACO Research Group, Department of Pharmaceutical Botany and Ecology, Faculty of Pharmacy, Charles University, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic.
authors.forename: Jakub
authors.initials: J
authors.lastname: Chlebek
authors.affiliation: †ADINACO Research Group, Department of Pharmaceutical Botany and Ecology, Faculty of Pharmacy, Charles University, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic.
authors.forename: Marcela
authors.initials: M
authors.lastname: Šafratová
authors.affiliation: †ADINACO Research Group, Department of Pharmaceutical Botany and Ecology, Faculty of Pharmacy, Charles University, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic.
authors.forename: Anna
authors.initials: A
authors.lastname: Hošt'álková
authors.affiliation: †ADINACO Research Group, Department of Pharmaceutical Botany and Ecology, Faculty of Pharmacy, Charles University, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic.
authors.forename: Lubomír
authors.initials: L
authors.lastname: Opletal
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000544:Alzheimer Disease / Q000188:drug therapy; D047151:Amaryllidaceae Alkaloids / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D015394:Molecular Structure
chemical_list: C459635:8-demethylmaritidine; D047151:Amaryllidaceae Alkaloids; D002800:Cholinesterase Inhibitors; C000601211:undulatine; D000110:Acetylcholinesterase