dc.contributor.author | Fernández Pampín, Natalia | |
dc.contributor.author | Vaquero Gutiérrez, Mónica | |
dc.contributor.author | Gil Antón, Tania | |
dc.contributor.author | Espino Ordóñez, Gustavo | |
dc.contributor.author | Fernández Zoppino, Darío | |
dc.contributor.author | García Ruiz, Begoña | |
dc.contributor.author | Busto Vázquez, Natalia | |
dc.date.accessioned | 2021-12-02T09:29:29Z | |
dc.date.available | 2021-12-02T09:29:29Z | |
dc.date.issued | 2022-01 | |
dc.identifier.issn | 0162-0134 | |
dc.identifier.uri | http://hdl.handle.net/10259/6253 | |
dc.description.abstract | Three 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.sponsorship | La 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.iso | eng | es |
dc.publisher | Elsevier | es |
dc.relation.ispartof | Journal of Inorganic Biochemistry. 2022, V. 226, 111663 | en |
dc.rights | Atribución 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | Cyclometalated platinum(II) complexes | en |
dc.subject | Clotrimazole | en |
dc.subject | Bifonazole | en |
dc.subject | Reactive oxygen species (ROS) | en |
dc.subject | Antitumoral | en |
dc.subject.other | Química inorgánica | es |
dc.subject.other | Chemistry, Inorganic | en |
dc.subject.other | Bioquímica | es |
dc.subject.other | Biochemistry | en |
dc.title | Distinct mechanism of action for antitumoral neutral cyclometalated Pt(II)-complexes bearing antifungal imidazolyl-based drugs | en |
dc.type | info:eu-repo/semantics/article | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.relation.publisherversion | https://doi.org/10.1016/j.jinorgbio.2021.111663 | es |
dc.identifier.doi | 10.1016/j.jinorgbio.2021.111663 | |
dc.relation.projectID | info: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.projectID | info:eu-repo/grantAgreement/Junta de Castilla y León//BU042U16 | |
dc.relation.projectID | info:eu-repo/grantAgreement/Junta de Castilla y León//BU305P18 | |
dc.relation.projectID | info:eu-repo/grantAgreement/Fundación Bancaria Caixa d'Estalvis i Pensions de Barcelona//LCF%2FPR%2FPR12%2F11070003 | |
dc.type.hasVersion | info:eu-repo/semantics/publishedVersion | es |
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