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

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.

Cancer cell-selective modulation of mitochondrial respiration and metabolism by potent organogold(iii) dithiocarbamates

“…6A and B). These complexes collectively are more cytotoxic towards the cell line MDA-MB-231 in comparison to the [C^N]Au(III)DTC complexes prepared by Bochmann et al 45 The different [C^N] backbone presented here proves to be a critical component in drug design and overall improvement of cytotoxic efficacy. The cytotoxicity of complexes 1a and 2a towards TNBC's is quite promising as these cell lines are typically cisplatin resistant.…”

“…S84-S103 †). Whereas gold dithiocarbamates are known to react with thiols, 45,49,51,69 detailed studies to unravel the potential mechanism of activity do not exist. HPLC trace of the reaction solution revealed one distinct band at a different retention time (R t -5.00 minutes) from 2a (R t -6.03 minutes) or GSH (R t -1.72 minutes) ( Fig.…”

“…27,[33][34][35][36] Among such complexes are Au(III)-2-pyridylmethanol, 37 Au(III)dichloro(N-ethylsalicylaldiminate), 38 Au(III)-phosphine, [39][40][41] cyclometalated Au(III), 27,34,[42][43][44][45][46] and Au(III)dithiocarbamates. 45,[47][48][49][50][51][52] Whereas different classes of Au(III)dithiocarbamate display promising anticancer activity in vitro and in vivo the mechanism of action is not well elucidated. 45,53 Herein, we report the synthesis of Au(III) dithiocarbamates that incorporate aryl-pyridine cyclometallation [C^N] ligands to improve complex stability and different aryl/alkyl dithiocarbamate ligands for structure activity relationship (SAR).…”

“…45,[47][48][49][50][51][52] Whereas different classes of Au(III)dithiocarbamate display promising anticancer activity in vitro and in vivo the mechanism of action is not well elucidated. 45,53 Herein, we report the synthesis of Au(III) dithiocarbamates that incorporate aryl-pyridine cyclometallation [C^N] ligands to improve complex stability and different aryl/alkyl dithiocarbamate ligands for structure activity relationship (SAR). The compounds display higher potency in a panel of cancer cells than cisplatin.…”

Iron (II) Polypyridyl Complexes as Antiglioblastoma Agents to Overcome the Blood-Brain Barrier and Inhibit Cell Proliferation by Regulating p53 and 4E-BP1 Pathways

“…Recently, researchers have investigated widely about metal-based complexes for cancer therapy, with various types of metallic antitumor candidates being developed for decades, such as gold (Au) and Au-NHCs complexes (Fung et al, 2017; Porchia et al, 2018; Williams et al, 2018), ruthenium (Ru) complexes (Tan et al, 2010), iridium (Ir) complexes (Cao et al, 2013), iron (Fe) complexes (Gou et al, 2016), etc. For instance, Che et al found that Au (III) complexes containing special ligand could act as smart fluorescent probes and anticancer agents (Zou et al, 2013).…”