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

Abstract

A series of novel J147 derivatives were synthesized, and their inhibitory activities against beta-amyloid (A beta) 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 A beta(42) oligomerization (IC50 = 17.3 mu M) and A beta(42) fibrillization (IC50 = 10.5 mu M), and disassembled the preformed A beta(42) fibrils with an EC50 of 10.2 mu M. Finally, we confirmed that 3j is also effective at preventing neurotoxicity induced by A beta(42)-oligomers as well as A beta(42)-fibrils.