Development of coumarin-inspired bifunctional hybrids as a new class of anti-Alzheimer's agents with potent in vivo efficacy.

ABSTRACT: Considering the multifactorial and complex nature of Alzheimer's disease and the requirement of an optimum multifunctional anti-Alzheimer's agent, a series of triazole tethered coumarin-eugenol hybrid molecules was designed as potential multifunctional anti-Alzheimer's agents using donepezil and a template. The designed hybrid molecules were synthesized via a click chemistry approach and preliminarily screened for cholinesterase and Aβ_1-42 aggregation inhibition. Among them, AS15 emerged as a selective inhibitor of AChE (IC₅₀ = 0.047 μM) over butyrylcholinesterase (BuChE: IC₅₀ ≥ 10 μM) with desired Aβ_1-42 aggregation inhibition (72.21% at 50 μM) properties. In addition, AS15 showed protective effects against DNA damage caused by hydroxyl r

SUBMITTER: Singh A 

PROVIDER: S-EPMC11707525 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature