Cyclometallated Au(III) dithiocarbamate complexes: synthesis, anticancer evaluation and mechanistic studies

Williams, Morwen, Bertrand, Benoît, Hughes, David L., Waller, Zoe Ann Ella, Schmidt, Claudia, Ott, Ingo, O'Connell, Maria Anne ORCID: https://orcid.org/0000-0002-0267-0951, Searcey, Mark ORCID: https://orcid.org/0000-0003-2273-8949 and Bochmann, Manfred ORCID: https://orcid.org/0000-0001-7736-5428 (2018) Cyclometallated Au(III) dithiocarbamate complexes: synthesis, anticancer evaluation and mechanistic studies. Metallomics, 10 (11). pp. 1655-1666. ISSN 1756-5901

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Abstract

A series of cationic mixed cyclometallated (C^N)Au(III) dithiocarbamate complexes has been synthesized in good yields [HC^N = 2-(p-t-butylphenyl)pyridine]. The crystal structure of [(C^N)AuS2CNEt2]PF6 (3) has been determined. The cytotoxic properties of the new complexes have been evaluated in vitro against a panel of human cancer cell lines and healthy cells and compared with a neutral mixed (C^C)Au(III) dithiocarbamate complex (C^C = 4,4′-di-t-butylbiphenyl-2,2′-diyl). The complexes appeared to be susceptible to reduction by glutathione but were stable in the presence of N-acetyl cysteine. The potential mechanism of action of this class of compounds has been investigated by measuring the intracellular uptake of some selected complexes, by determining their interactions with higher order DNA structures, and by assessing the ability to inhibit thioredoxin reductase. The complexes proved unable to induce the formation of reactive oxygen species. The investigations add to the picture of the possible mode of action of this class of complexes.

Item Type:	Article
Uncontrolled Keywords:	sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School:	Faculty of Science > School of Chemistry (former - to 2024) Faculty of Science > School of Pharmacy (former - to 2024)
UEA Research Groups:	Faculty of Science > Research Groups > Chemical Biology and Medicinal Chemistry (former - to 2021) Faculty of Science > Research Groups > Molecular and Tissue Pharmacology Faculty of Science > Research Groups > Chemistry of Light and Energy Faculty of Science > Research Groups > Chemistry of Materials and Catalysis
Depositing User:	LivePure Connector
Date Deposited:	24 Sep 2018 15:30
Last Modified:	25 Sep 2024 13:39
URI:	https://ueaeprints.uea.ac.uk/id/eprint/68338
DOI:	10.1039/C8MT00225H

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