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

La Manna, Sara, Roviello, Valentina, Monaco, Vittoria, Platts, James A. ORCID: https://orcid.org/0000-0002-1008-6595, Monti, Maria, Gabano, Elisabetta, Ravera, Mauro and Marasco, Daniela 2023. The inhibitory effects of platinum( ii ) complexes on amyloid aggregation: a theoretical and experimental approach. Dalton Transactions 52 , pp. 12677-12685. 10.1039/d3dt02187d

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Advanced Research Computing @ Cardiff (ARCCA) Chemistry
Additional Information:	License information from Publisher: LICENSE 1: URL: http://creativecommons.org/licenses/by-nc/3.0/, Start Date: 2023-08-25
Publisher:	Royal Society of Chemistry
ISSN:	1477-9226
Date of First Compliant Deposit:	4 September 2023
Date of Acceptance:	14 August 2023
Last Modified:	11 Jun 2024 14:55
URI:	https://orca.cardiff.ac.uk/id/eprint/162193

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