Alzheimer's disease (AD) is a neurodegenerative disorder with an increasing impact on society.
Because currently available therapy has only a short-term effect, a huge number of novel compounds
are developed every year exploiting knowledge of the various aspects of AD pathophysiology.
To better address the pathological complexity of AD, one of the most extensively pursued strategies by
medicinal chemists is based on multi-target-directed ligands (MTDLs). Donepezil is one of the currently
approved drugs for AD therapy acting as an acetylcholinesterase inhibitor. In this review, we
have made an extensive literature survey focusing on donepezil-derived MTDL hybrids primarily targeting
on different levels cholinesterases and amyloid beta (Aβ) peptide. The targeting includes direct
interaction of the compounds with Aβ, AChE-induced Aβ aggregation, inhibition of BACE-1 enzyme,
and modulation of biometal balance thus impeding Aβ assembly.
Keywords: Acetylcholinesterase, Alzheimer's disease, amyloid-β, biometal, beta-secretase 1, butyrylcholinesterase, multitarget
directed ligands, neuroprotection
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