Dual-target ligand discovery for Alzheimer's disease: triphenylphosphoranylidene derivatives as inhibitors of acetylcholinesterase and β-amyloid aggregation.

ABSTRACT: Alzheimer disease (AD) is one of the major neurodegenerative diseases that could not be prevented or completely cured and may lead to death. Here, we target AChE and β-amyloid proteins. Synthesising new triphenylphosphporanylidene derivatives based on the surveyed literature and testing their biological activity revealed promising results especially for the acetyl triphenylphosphoranylidene derivative 8c, which showed good inhibitor activity against AChE enzyme with IC₅₀ in the nanomolar range (97.04 nM); on the other hand, it showed poor selectivity for AChE versus butyrylcholinesterase but with some futural structural modification, this selectivity can be improved. 8c showed MMP-2 IC₅₀ of 724.19 nM and Aβ_1-42 aggregation IC₅₀ of 3

SUBMITTER: El-Hussieny M 

PROVIDER: S-EPMC9879200 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature