Donepezil-based rational design of <i>N</i>-substituted quinazolinthioacetamide candidates as potential acetylcholine esterase inhibitors for the treatment of Alzheimer's disease: <i>in vitro</i> and <i>in vivo</i> studies.

ABSTRACT: Alzheimer's disease (AD) stands as one of the most outstanding progressive neurodegenerative disorders. Obviously, acetylcholine esterase (AChE) is the primary enzyme responsible for breaking down acetylcholine (ACh) with a much more prominent effect than butyrylcholine esterase (BuChE). Hence, novel quinazoline derivatives (3a-p) were designed and synthesized as AChE inhibitors for AD treatment. The newly synthesized quinazoline derivatives (3a-p) were pursued for their inhibitory potential towards both AChE and BuChE. Notably, compound 3e displayed the highest inhibitory potential towards AChE (IC₅₀ = 9.26 nM) surpassing donepezil (IC₅₀ = 16.43 nM). On the other side, compound 3e effectively negated the decline in memory acquisition and retention instigated by ICV a

SUBMITTER: Al-Karmalawy AA 

PROVIDER: S-EPMC11865952 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature