Por favor, use este identificador para citar o enlazar este ítem: http://hdl.handle.net/10259/5340
Título
Cytotoxic Ag(I) and Au(I) NHC-carbenes bind DNA and show TrxR inhibition
Autor
Publicado en
Journal of Inorganic Biochemistry. 2020, V. 205, 110998
Editorial
Elsevier
Fecha de publicación
2020-04
ISSN
0162-0134
DOI
10.1016/j.jinorgbio.2020.110998
Resumen
A silver(I) and a gold(I) complex of the fluorescent N-heterocyclic carbenic (NHC) ligand 1-(9-anthracenylmethyl)-3-(3-trimethylsilyl-2-propynil)-benzimidazol-2-ylidene have been synthesized and characterized. These compounds show cytotoxicity in the micromolar range and higher antiproliferative properties than cisplatin (CDDP) against several tumour cell lines such as SW480 (colon), A549 (lung) and HepG2 (liver). Both metal complexes are successfully internalized by SW480 cells being the silver compound the most accumulated. Subsequently, they were evaluated as inhibitors of the selenoenzyme Thioredoxin reductase (TrxR) and as DNA binders. Fluorescence microscopy confirmed that both protein and DNA binding could be involved in the biological activity of the compounds. The silver carbene was the most effective enzyme inhibitor with an IC50 in the nanomolar range. Also, interaction studies with natural double stranded DNA highlight a strong stabilisation of the double helix after binding to the Ag(I) carbene, indicating its potential suitability as dual-targeting anticancer active molecule.
Palabras clave
Dual anticancer drug
Metal carbene complexes
Thioredoxin reductase
Anthracenyl dyes
DNA interactions
Materia
Bioquímica
Biochemistry
Versión del editor
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