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dc.contributor.author
Fernández Pampín, Natalia
dc.contributor.author
Vaquero, Mónica
dc.contributor.author
Gil, Tania
dc.contributor.author
Espino, Gustavo
dc.contributor.author
Fernández, Darío
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dc.contributor.author
García, Begoña
dc.contributor.author
Busto, Natalia
dc.date.available
2023-02-14T12:50:00Z
dc.date.issued
2022-01
dc.identifier.citation
Fernández Pampín, Natalia; Vaquero, Mónica; Gil, Tania; Espino, Gustavo; Fernández, Darío; et al.; Distinct mechanism of action for antitumoral neutral cyclometalated Pt(II)-complexes bearing antifungal imidazolyl-based drugs; Elsevier Science Inc.; Journal of Inorganic Biochemistry; 226; 1-2022; 1-10
dc.identifier.issn
0162-0134
dc.identifier.uri
http://hdl.handle.net/11336/187891
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.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Elsevier Science Inc.
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dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by/2.5/ar/
dc.subject
ANTITUMORAL
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BIFONAZOLE
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CLOTRIMAZOLE
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CYCLOMETALATED PLATINUM(II) COMPLEXES
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REACTIVE OXYGEN SPECIES (ROS)
dc.subject.classification
Bioquímica y Biología Molecular
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dc.subject.classification
Ciencias Biológicas
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dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
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dc.title
Distinct mechanism of action for antitumoral neutral cyclometalated Pt(II)-complexes bearing antifungal imidazolyl-based drugs
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2023-02-09T15:46:41Z
dc.journal.volume
226
dc.journal.pagination
1-10
dc.journal.pais
Estados Unidos
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dc.description.fil
Fil: Fernández Pampín, Natalia. Universidad de Burgos; España
dc.description.fil
Fil: Vaquero, Mónica. Universidad de Burgos; España
dc.description.fil
Fil: Gil, Tania. Universidad de Burgos; España
dc.description.fil
Fil: Espino, Gustavo. Universidad de Burgos; España
dc.description.fil
Fil: Fernández, Darío. Universidad de Burgos; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; Argentina
dc.description.fil
Fil: García, Begoña. Universidad de Burgos; España
dc.description.fil
Fil: Busto, Natalia. Universidad de Burgos; España
dc.journal.title
Journal of Inorganic Biochemistry
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dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.jinorgbio.2021.111663
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S016201342100310X
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