RT info:eu-repo/semantics/article
T1 Cytotoxic Ag(I) and Au(I) NHC-carbenes bind DNA and show TrxR inhibition
A1 Guarra, Federica
A1 Busto Vázquez, Natalia
A1 Guerri, Annalisa
A1 Marchetti, Lorella
A1 Marzo, Tiziano
A1 García Ruiz, Begoña
A1 Biver, Tarita
A1 Gabbiani, Chiara
K1 Dual anticancer drug
K1 Metal carbene complexes
K1 Thioredoxin reductase
K1 Anthracenyl dyes
K1 DNA interactions
K1 Bioquímica
K1 Biochemistry
AB 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.
PB Elsevier
SN 0162-0134
YR 2020
FD 2020-04
LK http://hdl.handle.net/10259/5340
UL http://hdl.handle.net/10259/5340
LA eng
NO “la Caixa” Foundation (LCF/PR/PR12/11070003), Ministerio de Ciencia Innovación y Universidades-FEDER (RTI2018-102040-B-100) and Junta de Castilla y León-FEDER (BU305P18).
DS Repositorio Institucional de la Universidad de Burgos
RD 23-nov-2024