Multifunctional heterometallic Iriii-Aui probes as promising anticancer and antiangiogenic agents

Redrado M. ; Benedi A. (Universidad de Zaragoza) ; Marzo I. (Universidad de Zaragoza) ; García-Otín A.L. ; Fernández-Moreira V. (Universidad de Zaragoza) ; Gimeno M. Concepción

Resumen: 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.

Idioma: Inglés

DOI: 10.1002/chem.202100707

Año: 2021

Publicado en: Chemistry - A European Journal 27, 38 (2021), 9885-9897
ISSN: 0947-6539

Factor impacto JCR: 5.02 (2021)

Categ. JCR: CHEMISTRY, MULTIDISCIPLINARY rank: 64 / 180 = 0.356 (2021) - Q2 - T2

Factor impacto CITESCORE: 9.1 - Chemical Engineering (Q1)

Factor impacto SCIMAGO: 1.343 - Chemistry (miscellaneous) (Q1) - Catalysis (Q1)

Financiación: info:eu-repo/grantAgreement/ES/DGA/B04-20R
Financiación: info:eu-repo/grantAgreement/ES/DGA-FSE/E07-20R
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/FIS-PI16-02112
Financiación: info:eu-repo/grantAgreement/ES/MCIU/PID2019-104379RB-C21
Financiación: info:eu-repo/grantAgreement/ES/MCIU/RED2018-102471-T
Financiación: info:eu-repo/grantAgreement/ES/MICINN/RYC-2018-025872-I

Tipo y forma: Article (Published version)

Área (Departamento): Área Química Inorgánica (Dpto. Química Inorgánica)
Área (Departamento): Área Bioquímica y Biolog.Mole. (Dpto. Bioq.Biolog.Mol. Celular)
Área (Departamento): Área Biología Celular (Dpto. Bioq.Biolog.Mol. Celular)