Conjugates of Tacrine with Salicylamide as Promising Multitarget Agents for Alzheimer's Disease.

ABSTRACT: New conjugates of tacrine and salicylamide with alkylene spacers were synthesized and evaluated as potential multifunctional agents for Alzheimer's disease (AD). The compounds exhibited high acetylcholinesterase (AChE, IC₅₀ to 0.224 μM) and butyrylcholinesterase (BChE, IC₅₀ to 0.0104 μM) inhibitory activities. They were also rather poor inhibitors of carboxylesterase, suggesting a low tendency to exert potential unwanted drug-drug interactions in clinical use. The conjugates were mixed-type reversible inhibitors of both cholinesterases and demonstrated dual binding to the catalytic and peripheral anionic sites of AChE in molecular docking that, along with experimental results on propidium iodide displacement, suggest their potential to block AChE-induced β-amyloid agg

SUBMITTER: Grishchenko MV 

PROVIDER: S-EPMC9314152 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature