Abstract
The deposition of human islet amyloid polypeptide (hIAPP) is considered as a causative factor of type 2 diabetes mellitus (T2DM). Developing effective inhibitors against the fibril formation of hIAPP is a potential way to treat T2DM. Recent studies indicate that various metal complexes including homo-binuclear Ru complexes can inhibit hIAPP aggregation. Hetero-multinuclear PtRu metal complexes exhibit multiple bioactivities, but their roles in reversing amyloidosis remain unclear. In this work, we synthesized and identified a new hetero-binuclear PtRu metal complex Na{[RuCl4(DMSO-S)](bpy)[Pt(DMSO-S)Cl2]} (bpy: 4,4′-bipyridyl). We studied the inhibitory effect of the compound on hIAPP aggregation together with K{[RuCl4(DMSO-S)](pyz)[Pt (DMSO-S)Cl2]} (pyz: pyrazine) through diverse biophysical methods. Results showed that two PtRu metal complexes can remarkably reverse hIAPP aggregation and scatter the fibrils into nanoscale particles. Thermodynamic and spectrometric studies revealed that the binding of metal complexes with hIAPP was a spontaneous, enthalpy-driven process resulting from the predominant hydrophobic interaction and metal coordination. Two hetero-binuclear PtRu metal complexes showed stronger binding affinity and better inhibitory effects against peptide fibril formation than homo-binuclear Ru complexes and corresponding mononuclear Ru complexes. The compounds also regulated the peptide-induced cytotoxicity against Insulinoma β-cells and significantly increased the cell viability. This work shed light on a potential strategy for designing hetero-multinuclear metal complexes against amyloidosis-related diseases.
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