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Multifunctional Donepezil Analogues As Cholinesterase And Bace1 Inhibitors, Keith D. Green, Marina Y. Fosso, Sylvie Garneau-Tsodikova

Pharmaceutical Sciences Faculty Publications

A series of 22 donepezil analogues were synthesized through alkylation/benzylation and compared to donepezil and its 6-O-desmethyl adduct. All the compounds were found to be potent inhibitors of both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), two enzymes responsible for the hydrolysis of the neurotransmitter acetylcholine in Alzheimer’s disease patient brains. Many of them displayed lower inhibitory concentrations of EeAChE (IC₅₀ = 0.016 ± 0.001 µM to 0.23 ± 0.03 µM) and EfBChE (IC₅₀ = 0.11 ± 0.01 µM to 1.3 ± 0.2 µM) than donepezil. One of the better compounds was tested against HsAChE and was …