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

다국어 초록 (Multilingual Abstract)

<P>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, <B>3j</B> with a 2,2-dicyanovinyl substituent showed the most potent inhibitory activity against Aβ<SUB>42</SUB> oligomerization (IC<SUB>50</SUB> = 17.3 μM) and Aβ<SUB>42</SUB> fibrillization (IC<SUB>50</SUB> = 10.5 μM), and disassembled the preformed Aβ<SUB>42</SUB> fibrils with an EC<SUB>50</SUB> of 10.2 μM. Finally, we confirmed that <B>3j</B> is also effective at preventing neurotoxicity induced by Aβ<SUB>42</SUB>-oligomers as well as Aβ<SUB>42</SUB>-fibrils.</P>

<P>Graphic Abstract</P><P>AJ147 derivative <B>3j</B> inhibits Aβ<SUB>42</SUB> oligomerization and fibrillization, disassembles the preformed Aβ<SUB>42</SUB> fibrils and prevents Aβ<SUB>42</SUB> induced neurotoxicity.
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