La Manna, Sara, Florio, Daniele, Platts, James  ORCID: https://orcid.org/0000-0002-1008-6595, Gabano, Elisabetta, Ravera, Mauro and Marasco, Daniela
2025.
The effects of Platinum(IV) complex on Aβ1-42 aggregation: a synergistic inhibition upon axial coordination.
Dalton Transactions
10.1039/D5DT00691K
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Abstract
Among novel metallodrugs, Pt(IV) complexes are receiving increasing attention as alternative to Pt(II) analogues since they exhibit higher kinetic inertness and, hence, fewer undesirable reactions. Pt(IV) complexes have been designed as prodrugs with mechanisms of action finely tuned by properties of the axial ligands. In this context, the insertion of known bioactive molecules as axial ligands to generate multi-target drugs (MTDs) is considered a valuable drug design strategy because of the possible synergistic effect between the metal centre and the organic moiety. By employing the repurposing of drugs in different diseases, in this study, the Pt(IV) complex (OC-6-44)-acetatodiamminedichlorido(4,5-dihydroxy-9,10-dioxo-9,10-dihydroanthracene-2-carboxylato)platinum(IV) was investigated for its ability to modulate the self-aggregation process of the amyloid peptide Aβ1-42. Specifically, the complex bears as ligand 4,5-dihydroxy-9,10-dioxo-9,10-dihydroanthracene-2-carboxylato (rhein) that is a natural aromatic molecule already known as discrete inhibitor of amyloid aggregation. Herein, several biophysical and microscopic assays, as Thioflavin T (ThT) fluorescence, Dynamic Light Scattering (DLS) and Scanning Electron (SEM) and confocal Microscopy, indicated that the Pt(IV) complex can inhibit and disassemble Aβ1-42 aggregation at a greater extent with respect to rhein alone. This effect was likely due to the formation of π–π interaction between the rhein moiety and the side chains of Aβ1-42 peptide. These experimental evidence was confirmed by molecular docking studies concerning monomeric and tetrameric Aβ1-42. Overall, the data support the application of Pt(IV) complexes as innovative neurotherapeutics.
| Item Type: | Article |
|---|---|
| Date Type: | Publication |
| Status: | Published |
| Schools: | Schools > Chemistry |
| Publisher: | Royal Society of Chemistry |
| ISSN: | 1477-9226 |
| Date of First Compliant Deposit: | 6 June 2025 |
| Date of Acceptance: | 28 May 2025 |
| Last Modified: | 13 Jun 2025 15:15 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/178851 |
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