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

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.

Modulation of Amyloidogenic Peptide Aggregation by Photoactivatable CO-Releasing Ruthenium(II) Complexes

“…Indeed, for compound 3 from t = 0 to t = 20 min, a slight increase of ThT signal is observable even though the enhancement is slower than that shown by the peptide alone and the ThT signal reaches intensities that are significantly lower than those found in the absence of complexes. A behavior similar to that reported for compound 3 has been observed for a Pt-compound that also acts as modulators of NPM1 264–277 aggregation [ 55 ]. The different behavior of the three Ru compounds here analyzed as modulators of aggregation should be related to their structural features.…”

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

“…Several studies outlined how the Aβ peptide/Cu interactions are mediated by the N-terminal region of Aβ-amyloid involving His 6 , His 13 , and His 14 and that these interactions modulate the aggregation and toxicity profiles of the entire Aβ 1–40 sequence [ 7 ]. In general, Pt(II) and Ru(III) [ 8 ] complexes are more stable and redox inert with respect to Zn-, Cu-, or Fe-based compounds, thus, they can have major chances of success to prevent toxic effects of Aβ oligomerization in a coordinative mechanism and to serve as potential neurodrugs [ 9 ]. Many investigations reported on the ability of Pt(II) complexes to interfere with amyloid aggregation.…”

“…Very recently, we carried out several studies focusing on the effects of several metallo-drugs on the aggregation of several peptide sequences assumed as amyloid models [ 20 , 21 , 22 , 23 , 24 , 25 ]. The fragment spanning 21–40 residues of the C-terminal domain of Aβ 1–40 (Aβ 21–40 , Table 1 ) was tested with Pd(II)-, Pt(II)- and Au(III) compounds featuring 2-(2′-pyridyl)benzimidazole [ 26 ], Pt(II) complexes with β-hydroxy dithiocinnamic esters [ 9 ] and Ru(II)-based CO-releasing molecules featuring bidentate benzimidazole and terpyridine derivatives [ 27 ]. They all revealed able to modulate self-assembly of different amyloid sequences employing coordination or oxidative mechanisms.…”

Plant isoquinoline alkaloids as potential neurodrugs: A comparative study of the effects of benzo[c]phenanthridine and berberine-based compounds on β-amyloid aggregation

“…The observed increase of Cotton effect for Aβ 1-42 in the presence of CO at 24 h ( Fig. 3 ) can be ascribed to a stabilization of these secondary structures [ [73] , [74] , [75] , [76] , [77] , [78] ]. When comparing the CD spectra of Aβ 1-42 in the presence of all three compounds after 24 h, it became apparent that the presence of the three isoquinoline alkaloids induced differences in the structural organization of Aβ 1-42 ( Fig.…”