Cyclometallated Au(iii) dithiocarbamate complexes: synthesis, anticancer evaluation and mechanistic studies. Issue 11 (26th September 2018)

• Record Type: Journal Article
• Authors: Williams, Morwen R. M.; Bertrand, Benoît; Hughes, David L.; Waller, Zoë A. E.; Schmidt, Claudia; Ott, Ingo; O'Connell, Maria; Searcey, Mark; Bochmann, Manfred
• Is Part Of: Metallomics. Volume 10:Issue 11(2018)
• Page Start: 1655
• Page End: 1666
• Publication Date: 2018-09-26
• Subjects: Metals -- Physiological effect -- Periodicals; 572.51
• DOI: 10.1039/c8mt00225h
• Languages: English
• ISSNs: 1756-5901

Abstract

Abstract : Investigations of the mechanism of action of cyclometallated Au(iii ) dithiocarbamate complexes highlighting new possible targets. 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)AuS2 CNEt2 ]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.