A Comparative Study of the Effects of Platinum (II) Complexes on β-Amyloid Aggregation: Potential Neurodrug Applications

Herein the effects of three platinum complexes, namely (SP-4-2)-(2,2 '-bipyridine)dichloridoplatinum(II), Pt-bpy, (SP-4-2)-dichlorido(1,10-phenanthroline) platinum(II), Pt-phen, and (SP-4-2)-chlorido(2,2 ':6 ',2 ''-terpyridine)platinum(II) chloride, Pt-terpy, on the aggregation of an amyloid model system derived from the C-terminal domain of A beta peptide (A beta(21-40)) were investigated. Thioflavin T (ThT) binding assays revealed the ability of Pt(II) compounds to repress amyloid aggregation in a dose-dependent way, whereas the ability of A beta(21-40) peptide to interfere with ligand field of metal complexes was analyzed through UV-Vis absorption spectroscopy and electrospray ionization mass spectrometry. Spectroscopic data provided micromolar EC50 values and allowed to assess that the observed inhibition of amyloid aggregation is due to the formation of adducts between A beta(21-40) peptide and complexes upon the release of labile ligands as chloride and that they can explore different modes of coordination toward A beta(21-40) with respect to the entire A beta(1-40) polypeptide. In addition, conformational studies through circular dichroism (CD) spectroscopy suggested that Pt-terpy induces soluble beta-structures of monomeric A beta(21-40), thus limiting self-recognition. Noticeably, Pt-terpy demonstrated the ability to reduce the cytotoxicity of amyloid peptide in human SH-SY5Y neuroblastoma cells. Presented data corroborate the hypothesis to enlarge the application field of already known metal-based agents to neurodegenerative diseases, as potential neurodrugs.

Automated summary

The effects of three platinum complexes on the aggregation of an amyloid model system were investigated, showing the ability of these compounds to repress amyloid aggregation and interact with the ligand field of Aβ peptide. Spectroscopic data and circular dichroism studies revealed that Pt-terpy induces soluble β-structures of monomeric Aβ(21-40) and reduces self-recognition, ultimately reducing cytotoxicity in human neuroblastoma cells. These findings suggest the potential application of metal-based agents as neurodrugs for neurodegenerative diseases.