117397 20230519145606.0 doi 10.1002/chem.202100707 sideral 127233 ART-2021-127233 eng Redrado M. (orcid)0000-0001-5201-0874 Multifunctional heterometallic Iriii-Aui probes as promising anticancer and antiangiogenic agents 2021 Access copy available to the general public Unrestricted A new class of emissive cyclometallated IrIII-AuI complexes with a bis(diphenylphosphino) methanide bridging ligand was successfully synthesised from the diphosphino complex [Ir(N^C)2(dppm)]+ (1). The different gold ancillary ligand, a triphenylphosphine (2), a chloride (3) or a thiocytosine (4) did not reveal any significant effect on the photophysical properties, which are mainly due to metal-to-ligand charge-transfer (3MLCT) transitions based on IrIII. However, the AuI fragment, along with the ancillary ligand, seemed crucial for the bioactivity in A549 lung carcinoma cells versus endothelial cells. Both cell types display variable sensitivities to the complexes (IC50=0.6–3.5 µM). The apoptotic pathway is activated in all cases, and paraptotic cell death seems to take place at initial stages in A549 cells. Species 2–4 showed at least dual lysosomal and mitochondrial biodistribution in A549 cells, with an initial lysosomal localisation and a possible trafficking process between both organelles with time. The bimetallic IrIII-AuI complexes disrupted the mitochondrial transmembrane potential in A549 cells and increased reactive oxygen species (ROS) generation and thioredoxin reductase (TrxR) inhibition in comparison with that displayed by the monometallic complex 1. Angiogenic activity assays performed in endothelial cells revealed the promising antimetastatic potential of 1, 2 and 4. © 2021 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH. info:eu-repo/grantAgreement/ES/DGA/B04-20R info:eu-repo/grantAgreement/ES/DGA-FSE/E07-20R info:eu-repo/grantAgreement/ES/ISCIII/FIS-PI16-02112 info:eu-repo/grantAgreement/ES/MCIU/PID2019-104379RB-C21 info:eu-repo/grantAgreement/ES/MCIU/RED2018-102471-T info:eu-repo/grantAgreement/ES/MICINN/RYC-2018-025872-I info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 5.02 2021 CHEMISTRY, MULTIDISCIPLINARY 64 / 180 = 0.356 2021 Q2 T2 1.343 2021 Chemistry (miscellaneous) 2021 Q1 Catalysis 2021 Q1 9.1 2021 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Benedi A. Universidad de Zaragoza Marzo I. Universidad de Zaragoza (orcid)0000-0002-2315-9079 García-Otín A.L. Fernández-Moreira V. Universidad de Zaragoza (orcid)0000-0002-1218-7218 Gimeno M. Concepción (orcid)0000-0003-0553-0695 2010 760 Universidad de Zaragoza Dpto. Química Inorgánica Área Química Inorgánica 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 1002 050 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Biología Celular 27, 38 (2021), 9885-9897 Chemistry (Weinh.) Chemistry - A European Journal 0947-6539 1997358 http://zaguan.unizar.es/record/117397/files/texto_completo.pdf Versión publicada 2895475 http://zaguan.unizar.es/record/117397/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:117397 articulos driver 2023-05-18-16:04:33 ARTICLE