The inhibitory effects of platinum(II) complexes on amyloid aggregation: a theoretical and experimental approach

Sara La Manna, Valentina Roviello, Vittoria Monaco, James A Platts, Maria Monti, Elisabetta GABANO, Mauro RAVERA, Daniela Marasco

Risultato della ricerca: Contributo su rivistaArticolo in rivistapeer review

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: Sup35p7-13 and NPM1264-277 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 π-π and π-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.
Lingua originaleInglese
pagine (da-a)12677-12685
Numero di pagine9
RivistaDalton Transactions
Volume52
Numero di pubblicazione36
DOI
Stato di pubblicazionePubblicato - 2023

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