Gold(I) and Silver(I) Complexes with 2-Anilinopyridine-Based Heterocycles as Multitarget Drugs against Colon Cancer

Mármol, I. ; Montanel-Perez, S. ; Royo, J.C. ; Gimeno, M.C. (Universidad de Zaragoza) ; Villacampa, M.D. ; Rodríguez-Yoldi, M.J. (Universidad de Zaragoza) ; Cerrada, E. (Universidad de Zaragoza)

Resumen: 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.

Idioma: Inglés

DOI: 10.1021/acs.inorgchem.0c02922

Año: 2020

Publicado en: Inorganic Chemistry 59, 23 (2020), 17732-17745
ISSN: 0020-1669

Factor impacto JCR: 5.165 (2020)

Categ. JCR: CHEMISTRY, INORGANIC & NUCLEAR rank: 5 / 45 = 0.111 (2020) - Q1 - T1

Factor impacto SCIMAGO: 1.348 - Chemistry (miscellaneous) (Q1) - Physical and Theoretical Chemistry (Q1) - Inorganic Chemistry (Q1)

Financiación: info:eu-repo/grantAgreement/ES/DGA/B16-R17
Financiación: info:eu-repo/grantAgreement/ES/DGA-FSE/E07-20R
Financiación: info:eu-repo/grantAgreement/ES/ISCIII-CIBERObn/CB06-03-1012
Financiación: info:eu-repo/grantAgreement/ES/MCIU/RED2018-102471-T
Financiación: info:eu-repo/grantAgreement/ES/MINECO/CTQ2016-75816-C2-1-P
Financiación: info:eu-repo/grantAgreement/ES/MINECO/PID2019-104379RB-C21
Financiación: info:eu-repo/grantAgreement/ES/MINECO/SAF2016-75441-R
Financiación: info:eu-repo/grantAgreement/EUR/SUDOE/INTERREG/Redvalue-SOE1-PI-E0123

Tipo y forma: Article (PostPrint)

Área (Departamento): Área Química Inorgánica (Dpto. Química Inorgánica)
Área (Departamento): Área Fisiología (Dpto. Farmacología y Fisiolog.)