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Design and synthesis of tacrine-quinone hybrids as multitarget ligands against Alzheimer's disease
Nepovimová, Eugenie ; Opletalová, Veronika (advisor) ; Musílek, Kamil (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Drug Control Student: Eugenie Nepovimová Supervisor: Assoc. Prof. RNDr. Veronika Opletalová, Ph.D. Title of Thesis: Design and synthesis of tacrine-quinone hybrids as multi-target ligands against Alzheimer's disease Alzheimer's disease (AD) is a multifactorial progressive neurodegenerative disorder that manifests as memory loss, personality changes, global cognitive dysfunction, and functional impairment. It is the leading cause of dementia in aged humans. Nowadays, there are no effective preventative measures, definitive diagnostic guidlines, or curative therapy for AD, its precise ethiology, too, remains unknown. To date, the pharmacotherapy of AD has relied on acetylcholinesterase (AChE) inhibitors - donepezil, rivastigmine and galantamine - and, more recently, on an N-methyl-D- aspartate (NMDA) receptor antagonist - memantine. Cholinesterase inhibitors enhance cholinergic transmission directly by inhibiting AChE which hydrolyses acetylcholine. Furthermore, it has been demonstrated that AChE plays an important role in Aβ-aggregation during the early stages of senile plaque formation, one of the hallmarks of AD. Therefore, AChE inhibition represents a critical target for the effective...
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