Gold(I) complexes based on nonsteroidal anti-inflammatory derivatives as multi-target drugs against colon cancer

Saez, Javier ; Quero, Javier (Universidad de Zaragoza) ; Rodriguez-Yoldi, María Jesús (Universidad de Zaragoza) ; Gimeno, M. Concepción ; Cerrada, Elena (Universidad de Zaragoza)

Resumen: Targeting inflammation and the molecules involved in the inflammatory process could be an effective cancer prevention and therapy strategy. Therefore, the use of anti-inflammatory strategies, such as NSAIDs and metal-based drugs, has become a promising approach for preventing and treating cancer by targeting multiple pathways involved in tumor progression. The present work describes new phosphane gold(I) complexes derived from nonsteroidal anti-inflammatory drugs as multitarget drugs against colon cancer. The antiproliferative effect of the most active complexes, [Au(L3)(JohnPhos)] (3b), [Au(L4)(CyJohnPhos)] (4a) and [Au(L4)(JohnPhos)] (4b) against colon cancer cells (Caco2-/TC7) seems to be mediated by the inhibition of the enzyme cyclooxygenase-1/2, modulation of reactive oxygen species levels by targeting thioredoxin reductase (TrxR) activity, and induction of apoptosis in cancer cells. Additionally, the three complexes exhibit high selectivity index values toward noncancerous cells. The research highlights the importance of maintaining cellular redox balance and the role of TrxR in cancer cell survival.

Idioma: Inglés

DOI: 10.1021/acs.inorgchem.4c02988

Año: 2024

Publicado en: Inorganic Chemistry 63, 42 (2024), 19769-19782
ISSN: 0020-1669

Financiación: info:eu-repo/grantAgreement/ES/DGA/B16-23R
Financiación: info:eu-repo/grantAgreement/ES/DGA/E07-23R
Financiación: info:eu-repo/grantAgreement/ES/ISCIII-CIBERObn/CB06-03-1012
Financiación: info:eu-repo/grantAgreement/ES/MICINN AEI/PID2022-136861NB-I00
Financiación: info:eu-repo/grantAgreement/EUR/SUDOE/INTERREG/NEWPOWER-S1-1.1-E01116

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Química Inorgánica (Dpto. Química Inorgánica)
Área (Departamento): Área Fisiología (Dpto. Farmac.Fisiol.y Med.L.F.)