Ruthenium(II) polypyridyl complex as inhibitor of acetylcholinesterase and Aβ aggregation

• Inhibition of acetylcholinesterase and Aβ (1–40) aggregation by ruthenium polypyridyl complexes has been evaluated.
• Kinetics and molecular modeling indicate significant role of ancillary ligand in their inhibitory potency.
• Complexes are nontoxic to human neuroblastoma cells.

Two ruthenium(II) polypyridyl complexes [Ru(phen)3]2+ (1) and [Ru(phen)2(bxbg)]2+ (2) (where phen = 1,10 phenanthroline, bxbg = bis(o-xylene)bipyridine glycoluril) have been evaluated for acetylcholinesterase (AChE) and Amyloid-β peptide (Aβ) aggregation inhibition. Complex 2 exhibits higher potency of AChE inhibition and kinetics and molecular modeling studies indicate that ancillary ligand plays significant role in inhibitory potency exhibited by complex 2. The inhibitory effect of these complexes on Aβ (1–40) aggregation is investigated using Thioflavin T fluorescence and Transmission Electron Microscopy. Both complexes efficiently inhibit Aβ (1–40) aggregation and are negligibly toxic to human neuroblastoma cells. This is the first demonstration that ruthenium(II) polypyridyl complexes simultaneously inhibit AChE and Aβ aggregation.

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