Title:Therapeutic Potential of Multifunctional Derivatives of Cholinesterase Inhibitors
Volume: 19
Issue: 8
Author(s): Maja Przybyłowska, Krystyna Dzierzbicka, Szymon Kowalski, Klaudia Chmielewska and Iwona Inkielewicz-Stepniak*
Affiliation:
- Department of Pharmaceutical Pathophysiology, Faculty of Pharmacy, Medical University of Gdansk, Gdansk,Poland
Keywords:
Tacrine, donepezil, galantamine, rivastigmine, multifunctional cholinesterase inhibitors, alzheimer's disease.
Abstract: The aim of this work is to review tacrine analogues from the last three years, which
were not included in the latest review work, donepezil and galantamine hybrids from 2015 and rivastigmine
derivatives from 2014. In this account, we summarize the efforts toward the development
and characterization of non-toxic inhibitors of cholinesterases based on mentioned drugs with
various interesting additional properties such as antioxidant, decreasing β-amyloid plaque aggregation,
nitric oxide production, pro-inflammatory cytokines release, monoamine oxidase-B activity,
cytotoxicity and oxidative stress in vitro and in animal model that classify these hybrids as potential
multifunctional therapeutic agents for Alzheimer’s disease. Moreover, herein, we have described
the cholinergic hypothesis, mechanisms of neurodegeneration and current pharmacotherapy
of Alzheimer’s disease based on the restoration of cholinergic function through blocking enzymes
that break down acetylcholine.