2024-03-28T18:10:11Zhttps://riubu.ubu.es/oai/requestoai:riubu.ubu.es:10259/53402022-04-29T22:42:07Zcom_10259_4365com_10259_5086com_10259_2604col_10259_4366
2020-06-10T12:29:12Z
urn:hdl:10259/5340
Cytotoxic Ag(I) and Au(I) NHC-carbenes bind DNA and show TrxR inhibition
Guarra, Federica
Busto Vázquez, Natalia
Guerri, Annalisa
Marchetti, Lorella
Marzo, Tiziano
García Ruiz, Begoña
Biver, Tarita
Gabbiani, Chiara
Dual anticancer drug
Metal carbene complexes
Thioredoxin reductase
Anthracenyl dyes
DNA interactions
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.
2020-06-10T12:29:12Z
2020-06-10T12:29:12Z
2020-04
info:eu-repo/semantics/article
0162-0134
http://hdl.handle.net/10259/5340
10.1016/j.jinorgbio.2020.110998
eng
Journal of Inorganic Biochemistry. 2020, V. 205, 110998
https://doi.org/10.1016/j.jinorgbio.2020.110998
info:eu-repo/grantAgreement/MICINN/RTI2018-102040-B-100
info:eu-repo/grantAgreement/JCyL/BU305P18
info:eu-repo/grantAgreement/FundaciónLaCaixa/LCF/PR/PR12/11070003
http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
Elsevier