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

Morwen Williams, Benoît Bertrand, David L. Hughes, Zoe Ann Ella Waller, Claudia Schmidt, Ingo Ott, Maria Anne O'Connell, Mark Searcey, Manfred Bochmann

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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.
Original languageEnglish
Pages (from-to)1655-1666
JournalMetallomics
Volume10
Issue number11
Early online date18 Sep 2018
DOIs
Publication statusPublished - 1 Nov 2018

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