Preliminary studies on trigonelline as potential anti-Alzheimer disease agent: Determination by hydrophilic interaction liquid chromatography and modeling of interactions with beta-amyloid

摘要

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.