Investigation of anti-cholinesterase and anti-amyloidogenic activities of β-lactam antibiotics

Abstract

Abstract Objectives Neuroinflammation is an important factor in the pathogenesis of neurodegenerative disesases. The following study aimed to clarify the effects of β-lactam antibiotics to the cholinergic system, on acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) activities, considering the structural differences of antibiotics, to evaluate the underlying mechanism of effects provided by protein-antibiotic interactions, and to clarify possible effects of the antibiotics on the aggregation of Aβ-peptides. Methods The inhibition/activation mechanisms for each antibiotic were examined kinetically by Ellman method. Destabilization effects of them on amyloid peptide fibrillation were examined and protein-ligand interactions were evaluated with most potent antibiotics by molecular docking studies. Results The most powerful inhibitions were detected by the inhibition studies of AChE with ceftazidime (CAZ) and BuChE with amoxicillin (AMX). CAZ was exhibited dose-related dual effect on AChE activity. CAZ was actually the dose-related modifier of AChE. At higher concentrations, CAZ was a nonessential activator of AChE. Molecular docking studies have been confirmed by kinetic studies. Interested β-lactam antibiotics did not prevent fibrillation rate as rifampicin. Conclusions Inhibition/activation behaviours of studied β-lactam antibiotics on both cholinesterases may suggest that cholinergic transmission is one of the crucially important components of the β-lactam antibiotics-induced central nervous system adverse reactions.