Dicyanovinyl-substituted J147 analogue inhibits oligomerization and fibrillation of β-amyloid peptides and protects neuronal cells from β-amyloid-induced cytotoxicity

摘要

A series of novel J147 derivatives were synthesized, and their inhibitory activities against β-amyloid (Aβ) aggregation and toxicity were evaluated by using the oligomer-specific antibody assay, the thioflavin-T fluorescence assay, and a cell viability assay in the transformed SH-SY5Y cell culture. Among the synthesized J147 derivatives, 3j with a 2,2-dicyanovinyl substituent showed the most potent inhibitory activity against Aβ_(42) oligomerization (IC_(50) = 17.3 μM) and Aβ_(42) fibrillization (IC_(50) = 10.5 μM), and disassembled the preformed Aβ_(42) fibrils with an EC_(50) of 10.2 μM. Finally, we confirmed that 3j is also effective at preventing neurotoxicity induced by Aβ_(42)-oligomers as well as Aβ_(42)-fibrils.