Anticancer gold(iii)-bisphosphine complex alters the mitochondrial electron transport chain to induce in vivo tumor inhibition

Abstract

Expanding the chemical diversity of metal complexes provides a robust platform to generate functional bioactive reagents.

Recent development of gold(i) and gold(iii) complexes as therapeutic agents for cancer diseases

“…Furthermore, it was relatively stable in the solution even in the presence of glutathione. 243 In 2021, Pozza et al reported two different piperidine dithiocarbamic acid (Pipe-DTC) Au( iii ) complexes. Complex 338 exhibited significant activity against HCT116 and AGS (adenocarcinoma gastric cell line) cells with IC 50 values of 1.1 ± 0.7 μM and 0.4 ± 0.2 μM, respectively 244 (Fig.…”

Gold(III)-P-chirogenic complex induces mitochondrial dysfunction in triple-negative breast cancer

“…Previous work from our laboratory have led to the development of gold-based small molecules with potent anticancer activity against different cancer cells ( Arojojoye et al., 2020 ; Kim et al., 2021 ; Mertens et al., 2020 ). Preliminary cellular response evoked by AuPhos-19 was differentiated from the other gold(I) compounds tested in our previous report.…”

“…Several gold complexes existing in Au (I) and (III) oxidation states have been reported to target thiol-containing enzymes (glutathione and thioredoxin reductase) ( Rigobello et al., 2004 ; Zou et al., 2015 ), proteasome deubiquitinases ( Milacic and Dou, 2009 ; Zou et al., 2016 ), and the mitochondria ( Barnard and Berners-Price, 2007 ; Rackham et al., 2007 ). Interestingly, some of these gold complexes have been reported to be potent against the clinically challenging TNBC both in vitro and in vivo ( Arojojoye et al., 2020 ; Kim et al., 2021 ; Mertens et al., 2020 ; Nardon et al., 2014 ; Ortega et al., 2020 ; Yeo et al., 2018 ). These developments highlight the potential that exist in developing gold-based compounds for chemotherapeutic application.…”

Auranofin and its analogs as prospective agents for the treatment of colorectal cancer

“…Several studies have pointed out that gold compounds cause their outstanding cytotoxic effects by taking advantage of multiple molecular and cellular mechanisms. The most credited mechanisms involve inhibition of thiol-containing enzymes, especially thioredoxin reductase (TrxR) [ 25 - 27 ] , direct mitochondrial damage [ 28 - 31 ] , or alteration of DNA functions [ 32 , 33 ] , all of which may contribute importantly to the observed anticancer actions. Although no non-platinum metal compound has been approved so far for clinical use, some gold drug candidates are being actively investigated.…”