The inhibitory effects of platinum(II) complexes on amyloid aggregation: a theoretical and experimental approach. in Dalton transactions (Cambridge, England : 2003) / Dalton Trans. 2023 Sep 19;52(36):12677-12685. doi: 10.1039/d3dt02187d.
2023
ASL Vercelli
Tipo pubblicazione
Journal Article
Autori/Collaboratori (8)Vedi tutti...
La Manna S
Department of Pharmacy, University of Naples Federico II, 80131, Naples, Italy. daniela.marasco@unina.it.
Roviello V
Department of Chemical, Materials, and Industrial Production Engineering (DICMaPI), University of Naples Federico II, 80125 Naples, Italy.
Monaco V
Department of Chemical Sciences, University of Naples Federico II, 80126, Naples, Italy.
et alii...
Abstract
Platinum (Pt)(II) square planar complexes are well-known anticancer drugs whose Mechanism of Action (MOA) are finely tuned by the polar, hydrophobic and aromatic features of the ligands. In the attempt to translate this tunability to the identification of potential neurodrugs, herein, four Pt(II) complexes were investigated in their ability to modulate the self-aggregation processes of two amyloidogenic models: Sup35p(7-13) and NPM1(264-277) peptides. In particular, phenanthriplatin revealed the most efficient agent in the modulation of amyloid aggregation: through several biophysical assays, as Thioflavin T (ThT), electrospray ionization mass spectrometry (ESI-MS) and ultraviolet-visible (UV-vis) absorption spectroscopy, this complex revealed able to markedly suppress aggregation and to disassemble small soluble aggregates. This effect was due to a direct coordination of phenanthriplatin to the amyloid, with the loss of several ligands and different stoichiometries, by the formation of ?-? and ?-cation interactions as indicated from molecular dynamic simulations. Presented data support a growing and recent approach concerning the repurposing of metallodrugs as potential novel neurotherapeutics.
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PMID : 37655459
DOI : 10.1039/d3dt02187d
Keywords
Organoplatinum Compounds/pharmacology; Amyloidogenic Proteins; Ligands; Platinum/pharmacology;