2026-09-09T12:01:00Zhttps://riubu.ubu.es/oai/request

oai:riubu.ubu.es:10259/62532024-07-25T07:33:04Zcom_10259_4363com_10259_5086com_10259_2604com_10259_4365com_10259_6256com_10259_9476com_10259.4_106col_10259_9477col_10259_4366col_10259_6257col_10259_4364

Fernández Pampín, Natalia Vaquero Gutiérrez, Mónica Gil Antón, Tania Espino Ordóñez, Gustavo Fernández Zoppino, Darío García Ruiz, Begoña Busto Vázquez, Natalia 2021-12-02T09:29:29Z 2021-12-02T09:29:29Z 2022-01 0162-0134 http://hdl.handle.net/10259/6253 10.1016/j.jinorgbio.2021.111663 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. 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). eng Elsevier Journal of Inorganic Biochemistry. 2022, V. 226, 111663 https://doi.org/10.1016/j.jinorgbio.2021.111663 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 info:eu-repo/grantAgreement/Junta de Castilla y León//BU042U16 info:eu-repo/grantAgreement/Junta de Castilla y León//BU305P18 info:eu-repo/grantAgreement/Fundación Bancaria Caixa d'Estalvis i Pensions de Barcelona//LCF%2FPR%2FPR12%2F11070003 Atribución 4.0 Internacional http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess Cyclometalated platinum(II) complexes Clotrimazole Bifonazole Reactive oxygen species (ROS) Antitumoral Química inorgánica Bioquímica Chemistry, Inorganic Biochemistry Distinct mechanism of action for antitumoral neutral cyclometalated Pt(II)-complexes bearing antifungal imidazolyl-based drugs info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion