Experimental study demonstrates inhibition of prion protein aggregation by ruthenium complexes in neuronal models, suggesting potential therapeutic applications.
Key Points
To synthesize and evaluate piano-stool ruthenium(II) complexes for their ability to inhibit the aggregation and cytotoxicity of human prion protein fragment PrP 106–126.
Synthesized RuBT and RuBI complexes using benzazole-quinoline scaffolds and determined their structures via X-ray crystallography.
Assessed anti-aggregation activity and seed-induced fibril formation of PrP 106–126 using ThT assays, circular dichroism, TEM, and AFM, complemented by molecular docking.
Evaluated neuroprotective properties against PrP 106–126 in HT-22 neuronal cells and anticancer cytotoxicity in SH-SY5Y neuroblastoma cells.
RuBT and RuBI exhibited strong binding affinity toward PrP 106–126, effectively preventing spontaneous and seeded amyloid fibril assembly.
Both ruthenium complexes conferred neuroprotection by reducing PrP 106–126-induced toxicity in HT-22 cells and demonstrated selective anticancer activity against SH-SY5Y cells.