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 29-mar-2024