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

Daniele Florio; Anna Maria Malfitano; Sarah Di Somma; Carolin Mügge; Wolfgang Weigand; Giarita Ferraro; Ilaria Iacobucci; Maria Monti; Giancarlo Morelli; Antonello Merlino; Daniela Marasco

doi:10.3390/ijms20040829

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.

Authors

Daniele Florio¹, Anna Maria Malfitano², Sarah Di Somma³, Carolin Mügge^{4

5}, Wolfgang Weigand⁶, Giarita Ferraro⁷, Ilaria Iacobucci^{8

9}, Maria Monti^{10

11}, Giancarlo Morelli¹², Antonello Merlino¹³, Daniela Marasco¹⁴

Affiliations

¹ Department of Pharmacy, University of Naples Federico II, Napoli 80134, Italy. [email protected].
² Department of Translational Medical Science, University of Naples Federico II, Napoli 80131, Italy. [email protected].
³ Department of Translational Medical Science, University of Naples Federico II, Napoli 80131, Italy. [email protected].
⁴ Institute for Inorganic and Analytical Chemistry, University of Jena, Jena 07743, Germany. [email protected].
⁵ Department of Biology, Ruhr-University Bochum, Bochum 44801, Germany. [email protected].
⁶ Institute for Inorganic and Analytical Chemistry, University of Jena, Jena 07743, Germany. [email protected].
⁷ Department of Chemical Sciences, University of Naples Federico II, Napoli 80126, Italy. [email protected].
⁸ Department of Chemical Sciences, University of Naples Federico II, Napoli 80126, Italy. [email protected].
⁹ CEINGE Biotecnologie Avanzate s.c.a r.l., University of Naples Federico II, Napoli 80145, Italy. [email protected].
¹⁰ Department of Chemical Sciences, University of Naples Federico II, Napoli 80126, Italy. [email protected].
¹¹ CEINGE Biotecnologie Avanzate s.c.a r.l., University of Naples Federico II, Napoli 80145, Italy. [email protected].
¹² Department of Pharmacy, University of Naples Federico II, Napoli 80134, Italy. [email protected].
¹³ Department of Chemical Sciences, University of Naples Federico II, Napoli 80126, Italy. [email protected].
¹⁴ Department of Pharmacy, University of Naples Federico II, Napoli 80134, Italy. [email protected].

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