Background: Alzheimer’s disease is progressive neurodegenerative disease incidence of
which has been steadily growing for past decades. Etiology of Alzheimer’s disease consists of
multiple micro and macroscopic changes and to this day is not satisfactorily understood.
Conventional therapy is based on inhibition of acetylcholinesterase of Alzheimer’s disease is
connected with considerable worldwide expenses.
Objective: Six clinically used cholinesterase inhibitors (donepezil, physostigmine, galanthamine,
huperzine A, rivastigmine and tacrine) and memantine were compared according to their cholinesterase
inhibitory properties. Additionally, the ability of tested compounds to directly inhibit protein aggregation as
well as the capability to promote the protein amyloid fibrils depolymerization was determined.
Method: Adopted colorimetric assay according to Ellman was used to evaluate the inhibition
aktivity against cholinesterases. The ability of compounds to influence agregation inhibition and
depolymerization activity was measured by means of thioflavin fluorescence assay.
Results: Huperzine A was found to be the most potent, highly selective acetylcholinesterase inhibitor.
Tacrine and physostigmine were the most potent butyrylcholinesterase inhibitors. Several inhibitors
showed some weak potency to affect protein fibrils aggregation or depolymerization. Namely
rivastigmine and galanthamine showed some effect on protein polymerization and depolymerization.
Conclusion: Data provided by experiments suggest that clinically used and standard cholinesterase
inhibitors influence the protein superstructures however the effect is weak. The need for novel structures
of cholinesterase inhibitors with sufficient protein aggregation inhibition and/or depolymerization is