title: Preliminary studies on trigonelline as potential anti-Alzheimer disease agent: determination by hydrophilic interaction liquid chromatography and modeling of interactions with beta-amyloid.
abstract: For trigonelline, a quaternary-base pyridine alkaloid of presumed Alzheimer's disease-preventing activity, a method of determination has been proposed, based on the hydrophilic interaction chromatography (HILIC). That method might be applied to study the agent's bioavailability, in particular its permeation through blood-brain barrier, which is an inevitable property for the potential central nervous system affecting drugs. Providing that trigonelline possesses the requested pharmacokinetic properties, once attaining pharmacodynamic phase it must interact effectively with the relevant molecular site in the brain, which is characteristic to neurodegenerative diseases, namely the beta-amyloid peptide. Here it was demonstrated by molecular modeling that affinity of trigonelline to the Aβ(1-42) peptide is high and similar to that of an anti-Alzheimer's disease drug candidate - cotinine.
authors.affiliation: Faculty of Chemistry, University of Gdańsk, Wita Stwosza 63, 80-952 Gdańsk, Poland. Electronic address: royek@chem.univ.gda.pl.
authors.forename: Joanna
authors.initials: J
authors.lastname: Makowska
authors.affiliation: Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdańsk, Gen. J. Hallera 107, 80-416 Gdańsk, Poland. Electronic address: dszczesny@gumed.edu.pl.
authors.forename: Damian
authors.initials: D
authors.lastname: Szczesny
authors.affiliation: Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdańsk, Gen. J. Hallera 107, 80-416 Gdańsk, Poland. Electronic address: agnieszkalichucka@gmail.com.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Lichucka
authors.affiliation: Faculty of Chemistry, University of Gdańsk, Wita Stwosza 63, 80-952 Gdańsk, Poland. Electronic address: lukasz@chem.univ.gda.pl.
authors.forename: Artur
authors.initials: A
authors.lastname: Giełdoń
authors.affiliation: Faculty of Chemistry, University of Gdańsk, Wita Stwosza 63, 80-952 Gdańsk, Poland. Electronic address: lech@chem.univ.gda.pl.
authors.forename: Lech
authors.initials: L
authors.lastname: Chmurzyński
authors.affiliation: Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdańsk, Gen. J. Hallera 107, 80-416 Gdańsk, Poland. Electronic address: roman.kaliszan@gumed.edu.pl.
authors.forename: Roman
authors.initials: R
authors.lastname: Kaliszan
mesh_terms: D000470:Alkaloids / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use; D000544:Alzheimer Disease / Q000188:drug therapy*; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D001682:Biological Availability; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002491:Central Nervous System Agents / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use; D002853:Chromatography, Liquid / Q000379:methods*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000470:Alkaloids; D016229:Amyloid beta-Peptides; D002491:Central Nervous System Agents; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C009560:trigonelline
keywords: Alzheimer disease; Aβ(1–42); Beta-amyloid; Docking; HILIC; Trigonelline