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Gold(I) and Silver(I) Complexes with 2-Anilinopyridine-Based Heterocycles as Multitarget Drugs against Colon Cancer.
Mármol, Inés; Montanel-Perez, Sara; Royo, José Carlos; Gimeno, M Concepción; Villacampa, M Dolores; Rodríguez-Yoldi, M Jesús; Cerrada, Elena.
Afiliação
  • Mármol I; Departamento de Química Inorgánica, Instituto de Síntesis Química y Catálisis Homogénea-ISQCH, Universidad de Zaragoza-CSIC, 50009 Zaragoza, Spain.
  • Montanel-Perez S; Departamento de Farmacología y Fisiología, Unidad de Fisiología. and CIBERobn, IIS Aragón, IA2, Universidad de Zaragoza, 50013 Zaragoza, Spain.
  • Royo JC; Departamento de Química Inorgánica, Instituto de Síntesis Química y Catálisis Homogénea-ISQCH, Universidad de Zaragoza-CSIC, 50009 Zaragoza, Spain.
  • Gimeno MC; Departamento de Farmacología y Fisiología, Unidad de Fisiología. and CIBERobn, IIS Aragón, IA2, Universidad de Zaragoza, 50013 Zaragoza, Spain.
  • Villacampa MD; Departamento de Química Inorgánica, Instituto de Síntesis Química y Catálisis Homogénea-ISQCH, Universidad de Zaragoza-CSIC, 50009 Zaragoza, Spain.
  • Rodríguez-Yoldi MJ; Departamento de Química Inorgánica, Instituto de Síntesis Química y Catálisis Homogénea-ISQCH, Universidad de Zaragoza-CSIC, 50009 Zaragoza, Spain.
  • Cerrada E; Departamento de Farmacología y Fisiología, Unidad de Fisiología. and CIBERobn, IIS Aragón, IA2, Universidad de Zaragoza, 50013 Zaragoza, Spain.
Inorg Chem ; 59(23): 17732-17745, 2020 Dec 07.
Article em En | MEDLINE | ID: mdl-33205964
ABSTRACT
A series of gold(I) and silver(I) derivatives with N- or S-donor ligands derived from 2-anilinopyridine has been synthesized and characterized. The mononuclear structure of [Au(L1)(PPh3)](TfO) (1a) and [Au(L2)(PPh3)](TfO) (1b) was confirmed by X-ray diffraction studies, as well as the dinuclear structure in the case of [Ag(TfO)(L1)]2 (4a). Most of the complexes are cytotoxic against a model of colorectal adenocarcinoma (Caco-2 cell line) and breast adenocarcinoma cancer cell lines (MCF-7). [Au(L1)(PPh3)](TfO) (1a) was able to induce caspases 8 and 3 activation, loss of mitochondrial membrane potential, and reactive oxygen species (ROS)-dependent cell death on Caco-2 cells upon 24 h incubation. In addition, the gold complex 1a produced a significant inhibition of the redox enzyme thioredoxin reductase as well as 20S proteasome. However, the silver(I) analogue, [Ag(TfO)(L1)(PPh3)] (2a), induced cell death independent of inhibition of thioredoxin reductase and 20S proteasome, triggered ROS-independent apoptosis mediated by caspase 8 and 3 activation, and loss of mitochondrial membrane potential, which points to a different mechanism of action for both derivatives, dependent on the metal center.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Piridinas / Prata / Complexos de Coordenação / Ouro / Compostos Heterocíclicos / Compostos de Anilina / Antineoplásicos Limite: Humans Idioma: En Revista: Inorg Chem Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Espanha

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Piridinas / Prata / Complexos de Coordenação / Ouro / Compostos Heterocíclicos / Compostos de Anilina / Antineoplásicos Limite: Humans Idioma: En Revista: Inorg Chem Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Espanha