Chemistry and biology of three representative gold(III) compounds as prospective anticancer agents

Aubipyc, i.e.[(bipydmb-H)Au(OH)][PF6] (where bipydmb-H = deprotonated 6-(1,1-dimethylbenzyl)-2,20- bipyridine), Auoxo6, i.e. [(bipy2Me)2Au2(l-O)2][PF6]2 (where bipy2Me = 6,60-dimethyl-2,20-bipyridine) and Au2phen i.e. [(phen2Me)2Au2(l-O)2][PF6]2 (where phen2Me = 2,9-dimethyl-1,10-phenanthroline), are three representative gold(III) compounds prepared and characterised in our laboratories during the last few years that manifested remarkable anticancer properties in vitro. Herein, the main chemical features of these compounds are summarised. Aubipyc is a mononuclear organogold(III) compound while Auoxo6 and Au2phen are binuclear gold(III) complexes. These compounds manifest a reasonable stability of their gold(III) chromophore in aqueous solutions at physiological pH; yet, a rather different redox behaviour was highlighted as Aubipyc displays high stability toward reduction while both Auoxo6 and Au2phen are rapidly reduced by ascorbic acid and glutathione. The antiproliferative properties of these gold(III) compounds were analysed in detail against a wide panel of human tumour cell lines. Remarkably, Auoxo6 and Au2phen revealed potent and rather similar patterns of antiproliferative actions while Aubipyc turned out to be less effective. For Auoxo6 and Au2phen more detailed biochemical studies are available documenting their effects on the proteome of treated cancer cells. Recent studies described the reactions of these gold compounds with various proteins at the molecular level; adduct formation was clearly documented in a few cases and their nature determined. Preliminary results suggest that these gold compounds may act as strong inhibitors of the selenoenzyme thioredoxin reductase and cause mitochondrial dysfunction. Based on the available in vitro data, these gold compounds look quite promising as prospective anticancer agents. Studies will soon be extended to assess their safety and efficacy in relevant animal models of cancer.