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Therapeutic Potential of Multifunctional Derivatives of Cholinesterase Inhibitors

[ Vol. 19 , Issue. 8 ]

Author(s):

Maja Przybyłowska, Krystyna Dzierzbicka, Szymon Kowalski, Klaudia Chmielewska and Iwona Inkielewicz-Stepniak*   Pages 1323 - 1344 ( 22 )

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.

Keywords:

Tacrine, donepezil, galantamine, rivastigmine, multifunctional cholinesterase inhibitors, alzheimer's disease.

Affiliation:

Department of Organic Chemistry, Faculty of Chemistry, Gdansk University of Technology, Gdansk, Department of Organic Chemistry, Faculty of Chemistry, Gdansk University of Technology, Gdansk, Department of Medicinal Chemistry, Medical University of Gdansk, Gdansk, Department of Organic Chemistry, Faculty of Chemistry, Gdansk University of Technology, Gdansk, Department of Pharmaceutical Pathophysiology, Faculty of Pharmacy, Medical University of Gdansk, Gdansk

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