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dc.contributor.authorFernández Pampín, Natalia 
dc.contributor.authorVaquero Gutiérrez, Mónica 
dc.contributor.authorGil Antón, Tania
dc.contributor.authorEspino Ordóñez, Gustavo 
dc.contributor.authorFernández Zoppino, Darío 
dc.contributor.authorGarcía Ruiz, Begoña 
dc.contributor.authorBusto Vázquez, Natalia 
dc.date.accessioned2021-12-02T09:29:29Z
dc.date.available2021-12-02T09:29:29Z
dc.date.issued2022-01
dc.identifier.issn0162-0134
dc.identifier.urihttp://hdl.handle.net/10259/6253
dc.description.abstractThree neutral Pt(II) complexes containing 1-Methylimidazole and the antifungal imidazolyl drugs Clotrimazole and Bifonazole have been prepared. The general formula of the new derivatives is [Pt(κ2-(C^N)Cl(L)], where C^N stands for ppy = 2-phenylpyridinate, and L = 1-Methylimidazole (MeIm) for [Pt-MeIm]; L = Clotrimazole (CTZ) for [Pt-CTZ] and L = Bifonazole (BFZ) for [Pt-BFZ]). The complexes have been completely characterized in solution and the crystal structures of [Pt-BFZ] and [Pt-CTZ] have been resolved. Complexes [Pt-MeIm] and [Pt-BFZ] present higher cytotoxicity than cisplatin in SW480 (colon adenocarcinoma), A549 (lung adenocarcinoma) and A2780 (ovarian cancer) cell lines. [Pt-MeIm] shows the highest accumulation in A549 cells, in agreement with its inability to interact with serum albumin. By contrast, [Pt-CTZ] and [Pt-BFZ] interact with serum proteins, a fact that reduces their bioavailability. The strongest interaction with bovine serum albumin (BSA) is found for [Pt-BFZ], which is the least internalized inside the cells. All the complexes are able to covalently interact with DNA. The most cytotoxic complexes, [Pt-MeIm] and [Pt-BFZ] induce cellular accumulation in G0/G1 and apoptosis by a similar pathway, probably involving a reactive oxygen species (ROS) generation mechanism. [Pt-BFZ] turns out to be the most efficient complex regarding ROS generation and causes mitochondrial membrane depolarization, whereas [Pt-MeIm] induces the opposite effect, hyperpolarization of the mitochondrial membrane. On the contrary, the least cytotoxic complex, [Pt-CTZ] cannot block the cell cycle or generate ROS and the mechanism by which it induces apoptosis could be a different one.en
dc.description.sponsorshipLa Caixa Foundation (LCF/PR/PR12/11070003), Consejería de Educación-Junta de Castilla y León-FEDER (BU042U16-BU305P18), Ministerio de Ciencia, Innovación y Universidades (RTI2018-102040-B-100). M.V. is grateful for the financial support received from the Consejería de Educación-Junta de Castilla y León-FEDER (BU042U16-BU305P18).en
dc.language.isoenges
dc.publisherElsevieres
dc.relation.ispartofJournal of Inorganic Biochemistry. 2022, V. 226, 111663en
dc.rightsAtribución 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectCyclometalated platinum(II) complexesen
dc.subjectClotrimazoleen
dc.subjectBifonazoleen
dc.subjectReactive oxygen species (ROS)en
dc.subjectAntitumoralen
dc.subject.otherQuímica inorgánicaes
dc.subject.otherChemistry, Inorganicen
dc.subject.otherBioquímicaes
dc.subject.otherBiochemistryen
dc.titleDistinct mechanism of action for antitumoral neutral cyclometalated Pt(II)-complexes bearing antifungal imidazolyl-based drugsen
dc.typeinfo:eu-repo/semantics/articlees
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses
dc.relation.publisherversionhttps://doi.org/10.1016/j.jinorgbio.2021.111663es
dc.identifier.doi10.1016/j.jinorgbio.2021.111663
dc.relation.projectIDinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-102040-B-I00/ES/PROPIEDADES ANTIMICROBIANAS DE NUEVOS COMPLEJOS ORGANOMETALICOS
dc.relation.projectIDinfo:eu-repo/grantAgreement/Junta de Castilla y León//BU042U16
dc.relation.projectIDinfo:eu-repo/grantAgreement/Junta de Castilla y León//BU305P18
dc.relation.projectIDinfo:eu-repo/grantAgreement/Fundación Bancaria Caixa d'Estalvis i Pensions de Barcelona//LCF%2FPR%2FPR12%2F11070003
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersiones


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