Gold(III) bis(thiosemicarbazonate) compounds in breast cancer cells: Cytotoxicity and thioredoxin reductase targeting
Entity
UAM. Departamento de Química InorgánicaPublisher
ElsevierDate
2018-03-25Citation
10.1016/j.ejmech.2018.02.009
European Journal of Medicinal Chemistry 148 (2018): 372-383
ISSN
0223-5234 (print)DOI
10.1016/j.ejmech.2018.02.009Funded by
This research was supported by the EC (FP7-PEOPLE-2013-CIG, no. 631396), the MINECO of Spain (RYC-2012-11231, and CTQ2014-60100-R), the Instituto de Salud Carlos III (PS09/00963), and the Comunidad Autonoma de Madrid (S2013/MIT-2850)Project
info:eu-repo/grantAgreement/EC/FP7/631396/EU//MEMOTUMCELLMACH; Gobierno de España. CTQ2014-60100-REditor's Version
https://doi.org/10.1016/j.ejmech.2018.02.009Subjects
Cisplatin; Gold(III); Thiosemicarbazones; Reactive Oxygen Species; Thioredoxin Reductase; QuímicaRights
© 2018 Elsevier Masson SAS.Esta obra está bajo una licencia de Creative Commons Reconocimiento-NoComercial-SinObraDerivada 4.0 Internacional.
Abstract
Gold(III) compounds have received increasing attention in cancer research. Three gold complexes of general formula [AuIIIL]Cl, where L is benzil bis(thiosemicarbazonate), compound 1, benzil bis(4-methyl-3-thiosemicarbazonate), compound 2, or benzil bis(4-cyclohexyl-3-thiosemicarbazonate), compound 3, have been synthesized and fully characterized, including the X-ray crystal structure of compound 3, confirming square-planar geometry around the gold(III) centre. Compound 1 showed moderate cytotoxicity and accumulation in MCF7 breast cancer cells but did not inhibit thioredoxin reductase (TrxR) activity and did not induce reactive oxygen species (ROS) production. Compound 2, the least cytotoxic, was found to be capable of modestly inhibiting TrxR activity and produced low levels of ROS in the MCF7 cell line. The most cytotoxic compound, 3, had the highest cellular accumulation and its distribution pattern showed a clear preference for the cytosol and mitochondria of MCF7 cells. It readily hampered intracellular TrxR activity leading to a dramatic alteration of the cellular redox state and to the induction of cell death
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Google Scholar:Rodríguez Fanjul, Vanessa
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López Torres, Elena Sofía
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Mendiola Martín, María Antonia
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Pizarro, Ana María
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