A Diruthenium Metallodrug as a Potent Inhibitor of Amyloid-β Aggregation: Synergism of Mechanisms of Action

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dc.contributor.authorLa Manna, Sara
dc.contributor.authorDi Natale, Concetta
dc.contributor.authorPanzetta, Valeria
dc.contributor.authorLeone, Marilisa
dc.contributor.authorMercurio, Flavia
dc.contributor.authorCipollone, Irene
dc.contributor.authorMonti, Maria
dc.contributor.authorNetti, Paolo
dc.contributor.authorFerraro, Giarita
dc.contributor.authorTerán More, Aaron
dc.contributor.authorSánchez Peláez, Ana Edilia
dc.contributor.authorHerrero Domínguez, Santiago
dc.contributor.authorMerlino, Antonello
dc.contributor.authorMarasco, Daniela
dc.date.accessioned2024-01-15T15:56:55Z
dc.date.available2024-01-15T15:56:55Z
dc.date.issued2024
dc.description.abstractThe physical and chemical properties of paddlewheel diruthenium compounds are highly dependent on the nature of the ligands surrounding the bimetallic core. Herein, we compare the ability of two diruthenium compounds, [Ru2Cl(D-p-FPhF)- (O2CCH3)3]·H2O (1) (D-p-FPhF− = N,N′-bis(4-fluorophenyl)- formamidinate) and K3[Ru2(O2CO)4]·3H2O (2), to act as inhibitors of amyloid aggregation of the Aβ1−42 peptide and its peculiar fragments, Aβ1−16 and Aβ21−40. A wide range of biophysical techniques has been used to determine the inhibition capacity against aggregation and the possible mechanism of action of these compounds (Thioflavin T fluorescence and autofluorescence assays, UV−vis absorption spectroscopy, circular dichroism, nuclear magnetic resonance, mass spectrometry, and electron scanning microscopy). Data show that the most effective inhibitory effect is shown for compound 1. This compound inhibits fiber formation and completely abolishes the cytotoxicity of Aβ1−42. The antiaggregatory capacity of this complex can be explained by a binding mechanism of the dimetallic units to the peptide chain along with π−π interactions between the formamidinate ligand and the aromatic side chains. The results suggest the potential use of paddlewheel diruthenium complexes as neurodrugs and confirm the importance of the steric and charge effects on the properties of diruthenium compounds
dc.description.departmentDepto. de Química Inorgánica
dc.description.facultyFac. de Ciencias Químicas
dc.description.refereedTRUE
dc.description.sponsorshipUniversidad Complutense de Madrid
dc.description.sponsorshipMinisterio de Ciencia e Innovación (España)
dc.description.statuspub
dc.identifier.citationSara La Manna, Concetta Di Natale, Valeria Panzetta, Marilisa Leone, Flavia A. Mercurio, Irene Cipollone, Maria Monti, Paolo A. Netti, Giarita Ferraro, Aarón Terán, Ana E. Sánchez-Peláez, Santiago Herrero, Antonello Merlino, and Daniela Marasco Inorganic Chemistry 2024 63 (1), 564-575 DOI: 10.1021/acs.inorgchem.3c03441
dc.identifier.doi10.1021/acs.inorgchem.3c03441
dc.identifier.issn0020-1669
dc.identifier.officialurlhttps://doi.org/10.1021/acs.inorgchem.3c03441
dc.identifier.urihttps://hdl.handle.net/20.500.14352/93172
dc.issue.number1
dc.journal.titleInorganic Chemistry
dc.language.isoeng
dc.page.final575
dc.page.initial564
dc.publisherAmerican Chemical Society
dc.relation.projectID(GRFN32/23 and PR3/ 23-30828)
dc.relation.projectIDPredoctoral Grant (CT63/19-CT64/19) and Research Stay Grant (EB25/22) a
dc.relation.projectIDPostgraduate Fellowship at Residencia de Estudiantes (2021−2022)
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.cdu546
dc.subject.keywordCircular dichroism spectroscopy
dc.subject.keywordDichroism
dc.subject.keywordGlycoproteins
dc.subject.keywordLigands
dc.subject.keywordMass spectrometry
dc.subject.keywordNuclear magnetic resonance spectroscopy
dc.subject.keywordPeptides
dc.subject.keywordUltraviolet spectroscopy
dc.subject.ucmQuímica
dc.subject.unesco2303 Química Inorgánica
dc.titleA Diruthenium Metallodrug as a Potent Inhibitor of Amyloid-β Aggregation: Synergism of Mechanisms of Action
dc.typejournal article
dc.type.hasVersionVoR
dc.volume.number63
dspace.entity.typePublication
relation.isAuthorOfPublicationa154643d-eb94-4c49-9bbe-abbcfb7bf515
relation.isAuthorOfPublicationb5123288-82d8-4996-8d90-b65b7afa53d9
relation.isAuthorOfPublication59924d8b-089e-42db-b835-600c5cee5487
relation.isAuthorOfPublication.latestForDiscoverya154643d-eb94-4c49-9bbe-abbcfb7bf515
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