Combining Experimental and Computational Methods to Produce Conjugates of Anticholinesterase and Antioxidant Pharmacophores with Linker Chemistries Affecting Biological Activities Related to Treatment of Alzheimer's Disease.

ABSTRACT: Effective therapeutics for Alzheimer's disease (AD) are in great demand worldwide. In our previous work, we responded to this need by synthesizing novel drug candidates consisting of 4-amino-2,3-polymethylenequinolines conjugated with butylated hydroxytoluene via fixed-length alkylimine or alkylamine linkers (spacers) and studying their bioactivities pertaining to AD treatment. Here, we report significant extensions of these studies, including the use of variable-length spacers and more detailed biological characterizations. Conjugates were potent inhibitors of acetylcholinesterase (AChE, the most active was 17d IC₅₀ 15.1 ± 0.2 nM) and butyrylcholinesterase (BChE, the most active was 18d: IC₅₀ 5.96 ± 0.58 nM), with weak inhibition of off-target carboxyle

SUBMITTER: Makhaeva GF 

PROVIDER: S-EPMC10820264 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature