Platinum(II) O, S Complexes Inhibit the Aggregation of Amyloid Model Systems

Int J Mol Sci. 2019 Feb 14;20(4):829. doi: 10.3390/ijms20040829.

Abstract

Platinum(II) complexes with different cinnamic acid derivatives as ligands were investigated for their ability to inhibit the aggregation process of amyloid systems derived from Aβ, Yeast Prion Protein Sup35p and the C-terminal domain of nucleophosmin 1. Thioflavin T binding assays and circular dichroism data indicate that these compounds strongly inhibit the aggregation of investigated peptides exhibiting IC50 values in the micromolar range. MS analysis confirms the formation of adducts between peptides and Pt(II) complexes that are also able to reduce amyloid cytotoxicity in human SH-SY5Y neuroblastoma cells. Overall data suggests that bidentate ligands based on β-hydroxy dithiocinnamic esters can be used to develop platinum or platinoid compounds with anti-amyloid aggregation properties.

Keywords: amyloid aggregation; anti-aggregation properties; platinum complexes.

MeSH terms

  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / antagonists & inhibitors
  • Amyloid beta-Peptides / chemical synthesis
  • Amyloid beta-Peptides / chemistry*
  • Amyloidosis / drug therapy
  • Amyloidosis / pathology
  • Benzothiazoles / pharmacology
  • Cell Line
  • Cinnamates / chemistry
  • Cinnamates / pharmacology
  • Circular Dichroism
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacology*
  • Humans
  • Ligands
  • Nuclear Proteins / antagonists & inhibitors
  • Nuclear Proteins / chemistry*
  • Nucleophosmin
  • Peptide Termination Factors / antagonists & inhibitors
  • Peptide Termination Factors / chemistry*
  • Platinum / chemistry
  • Platinum / pharmacology
  • Protein Aggregation, Pathological / drug therapy*
  • Protein Aggregation, Pathological / genetics
  • Protein Aggregation, Pathological / pathology
  • Saccharomyces cerevisiae Proteins / antagonists & inhibitors
  • Saccharomyces cerevisiae Proteins / chemistry*

Substances

  • Amyloid beta-Peptides
  • Benzothiazoles
  • Cinnamates
  • Coordination Complexes
  • Ligands
  • NPM1 protein, human
  • Nuclear Proteins
  • Peptide Termination Factors
  • SUP35 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Nucleophosmin
  • cinnamic acid
  • thioflavin T
  • Platinum