Conjugates of amiridine and salicylic derivatives as promising multifunctional CNS agents for potential treatment of Alzheimer's disease.

ABSTRACT: New conjugates of amiridine and salicylic derivatives (salicylamide, salicylimine, and salicylamine) with different lengths of alkylene spacers were designed, synthesized, and evaluated as potential multifunctional central nervous system therapeutic agents for Alzheimer's disease (AD). Conjugates demonstrated high acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition (IC₅₀: AChE, 0.265-4.24 μM; BChE, 0.01-0.64 μM) but poor activity against off-target carboxylesterase (CES). Specifically, conjugates with a (CH₂)₈ spacer showed the highest AChE and BChE inhibition: 3-16 times more effective than amiridine. Salicylamides 7b and 7c had the maximum BChE/AChE selectivity ratios: 193 and 138, respectively. Conjugates were mixed-type reversible in

SUBMITTER: Makhaeva GF 

PROVIDER: S-EPMC11650361 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature