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Profiling donepezil template into multipotent hybrids with antioxidant properties

E. Mezeiova, K. Spilovska, E. Nepovimova, L. Gorecki, O. Soukup, R. Dolezal, D. Malinak, J. Janockova, D. Jun, K. Kuca, J. Korabecny,

. 2018 ; 33 (1) : 583-606.

Language English Country England, Great Britain

Document type Journal Article, Review

Persistent link   https://www.medvik.cz/link/bmc18024309

Grant support
NV15-30954A MZ0 CEP Register

Alzheimer's disease is debilitating neurodegenerative disorder in the elderly. Current therapy relies on administration of acetylcholinesterase inhibitors (AChEIs) -donepezil, rivastigmine, galantamine, and N-methyl-d-aspartate receptor antagonist memantine. However, their therapeutic effect is only short-term and stabilizes cognitive functions for up to 2 years. Given this drawback together with other pathological hallmarks of the disease taken into consideration, novel approaches have recently emerged to better cope with AD onset or its progression. One such strategy implies broadening the biological profile of AChEIs into so-called multi-target directed ligands (MTDLs). In this review article, we made comprehensive literature survey emphasising on donepezil template which was structurally converted into plethora of MTLDs preserving anti-cholinesterase effect and, at the same time, escalating the anti-oxidant potential, which was reported as a crucial role in the pathogenesis of the Alzheimer's disease.

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$a Alzheimer's disease is debilitating neurodegenerative disorder in the elderly. Current therapy relies on administration of acetylcholinesterase inhibitors (AChEIs) -donepezil, rivastigmine, galantamine, and N-methyl-d-aspartate receptor antagonist memantine. However, their therapeutic effect is only short-term and stabilizes cognitive functions for up to 2 years. Given this drawback together with other pathological hallmarks of the disease taken into consideration, novel approaches have recently emerged to better cope with AD onset or its progression. One such strategy implies broadening the biological profile of AChEIs into so-called multi-target directed ligands (MTDLs). In this review article, we made comprehensive literature survey emphasising on donepezil template which was structurally converted into plethora of MTLDs preserving anti-cholinesterase effect and, at the same time, escalating the anti-oxidant potential, which was reported as a crucial role in the pathogenesis of the Alzheimer's disease.
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$a Nepovimova, Eugenie $u a Biomedical Research Centre, University Hospital Hradec Kralove , Hradec Kralove , Czech Republic. c Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences , Hradec Kralove , Czech Republic. d Department of Chemistry , University of Hradec Kralove , Hradec Kralove , Czech Republic.
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$a Górecki, Lukáš $7 xx0243228 $u a Biomedical Research Centre, University Hospital Hradec Kralove , Hradec Kralove , Czech Republic. c Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences , Hradec Kralove , Czech Republic.
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$a Dolezal, Rafael $u a Biomedical Research Centre, University Hospital Hradec Kralove , Hradec Kralove , Czech Republic.
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