2026-04-17T12:11:18Zhttps://riubu.ubu.es/oai/request

oai:riubu.ubu.es:10259/75612023-04-19T08:00:45Zcom_10259_4365com_10259_5086com_10259_2604com_10259_4363com_10259_6185com_10259_3591com_10259.4_106col_10259_4366col_10259_4364col_10259_6186

Acuña, M. Isabel 2e343025-181b-40c0-8d54-03bd6f18af57 600 Rubio Antolin, Ana Rosa 491 600 0000-0002-8504-9692 Martínez Alonso, Marta 772 600 0000-0002-0931-5274 Busto Vázquez, Natalia 83 600 0000-0001-9637-1209 Rodríguez, Ana María acb36428-a2da-4e1b-a8d8-1f616e7c00b5 600 Davila Ferreira, Nerea 838e64a3-dde1-4b34-b260-e0fd35b70b36 600 Smythe, Carl b78e6582-65fe-4307-b274-dfe4143fa992 600 Espino Ordóñez, Gustavo 162 600 0000-0001-5617-5705 García Ruiz, Begoña 217 600 0000-0002-0817-1651 Domínguez, Fernando b2bd4d22-043f-4d2e-b221-825845d10230 600 2023-03-20T10:47:17Z 2023-03-20T10:47:17Z 2022-12 http://hdl.handle.net/10259/7561 10.3390/cancers15010107 2072-6694 Cancers are driven by multiple genetic mutations but evolve to evade treatments targeting specific mutations. Nonetheless, cancers cannot evade a treatment that targets mitochondria, which are essential for tumor progression. Iridium complexes have shown anticancer properties, but they lack specificity for their intracellular targets, leading to undesirable side effects. Herein we present a systematic study on structure-activity relationships of eight arylbenzazole-based Iridium(III) complexes of type [IrCl(Cp*)], that have revealed the role of each atom of the ancillary ligand in the physical chemistry properties, cytotoxicity and mechanism of biological action. Neutral complexes, especially those bearing phenylbenzimidazole (HL1 and HL2), restrict the binding to DNA and albumin. One of them, complex 1[C,NH-Cl], is the most selective one, does not bind DNA, targets exclusively the mitochondria, disturbs the mitochondria membrane permeability inducing proton leak and increases ROS levels, triggering the molecular machinery of regulated cell death. In mice with orthotopic lung tumors, the administration of complex 1[C,NH-Cl] reduced the tumor burden. Cancers are more vulnerable than normal tissues to a treatment that harnesses mitochondrial dysfunction. Thus, complex 1[C,NH-Cl] characterization opens the way to the development of new compounds to exploit this vulnerability We acknowledge the “la Caixa” Foundation (LCF/PR/PR12/11070003), Ministerio de Ciencia Innovación y Universidades-FEDER (RTI2018-102040-B-100) and Junta de Castilla y León-FEDER (BU305P18) for financial support. Networking support by COST Action CA18202 (NECTAR) is also acknowledged. application/pdf eng MDPI Cancers. 2022, V. 15, n. 1, 107 https://doi.org/10.3390/cancers15010107 info:eu-repo/grantAgreement/Fundación Bancaria Caixa d'Estalvis i Pensions de Barcelona//LCF%2FPR%2FPR12%2F11070003// 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//BU305P18//DISEÑO Y CARACTERIZACIÓN DE COMPLEJOS BIOINORGÁNICOS Y CLÚSTERES CUÁNTICOS ATÓMICOS. PROPIEDADES ANTIMICROBIANAS EN CEPAS RESISTENTES. PROPIEDADES ANTITUMORALES EN LA OSCURIDAD Y BAJO IRRADIACIÓN/ info:eu-repo/grantAgreement/COST//CA18202/EU/Network for Equilibria and Chemical Thermodynamics Advanced Research/NECTAR/ Atribución 4.0 Internacional http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess Organometallic iridium complex DNA binding Mitochondrial damage Proton leak Apoptosis Química física Physiology Chemistry, Physical and theoretical Fisiología Medicina Medicine Targets, Mechanisms and Cytotoxicity of Half-Sandwich Ir(III) Complexes Are Modulated by Structural Modifications on the Benzazole Ancillary Ligand info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Cancers 15 1 THUMBNAIL Acuña-Cancers_2022.pdf.jpg Acuña-Cancers_2022.pdf.jpg IM Thumbnail image/jpeg 3393 https://riubu.ubu.es/bitstream/10259/7561/4/Acu%c3%b1a-Cancers_2022.pdf.jpg f163b84775a604e32c157ab2d65f466d MD5 4 LICENSE license.txt license.txt text/plain; charset=utf-8 1362 https://riubu.ubu.es/bitstream/10259/7561/3/license.txt 5d013bfa6e473ff0db22cd82a4d71a70 MD5 3 CC-LICENSE license_rdf license_rdf application/rdf+xml; charset=utf-8 908 https://riubu.ubu.es/bitstream/10259/7561/2/license_rdf 0175ea4a2d4caec4bbcc37e300941108 MD5 2 ORIGINAL Acuña-Cancers_2022.pdf Acuña-Cancers_2022.pdf application/pdf 3779876 https://riubu.ubu.es/bitstream/10259/7561/1/Acu%c3%b1a-Cancers_2022.pdf 1a36ad7b4171bf0497fb8498219712ea MD5 1 10259/7561 oai:riubu.ubu.es:10259/7561 2023-04-19 10:00:45.901 Repositorio Institucional de la Universidad de Burgos bubrep@ubu.es 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