On the path to gold: Monoanionic Au bisdithiolate complexes with antimicrobial and antitumor activities

The emergence of resistance to antimicrobial and anticancer drugs poses severe threats to public health worldwide, highlighting the need for more efficient treatments. Here, four monoanionic Au bisdithiolate complexes [Au(mnt)₂]^- (where mnt = 1,1-dicyanoethylene-2,2-dithiolate)(1), [Au(i-mnt)₂]^- (where i-mnt = 2,2-dicyanoethylene-1,1-dithiolate)(2), [Au(cdc)₂]^- (where cdc = cyanodithioimido carbonate)(3), and [Au(qdt)₂]^- (where qdt = quinoxaline-2,3-dithiolate)(4) were screened for their antimicrobial and antitumor activities. Complexes 3 and 4 showed antibacterial activity against Staphylococcus aureus [minimal inhibitory concentration (MIC) = 15.3 and 14.7 μg/mL, respectively]. Complex 3 also caused significant growth inhibition of Candida glabrata (MIC = 7.0 μg/mL). Concentrations of complexes 1-4 up to 125 μg/mL had no growth inhibition activity against Escherichia coli. The cytotoxic activity of complexes 1-4 was evaluated against the ovarian cancer cells A2780 and A2780cisR, sensitive and resistant to cisplatin, respectively. All compounds showed high cytotoxic activities against both tumoral cell lines, exhibiting IC₅₀ values in the low micromolar range (0.9-5.5 μM) upon 48 h incubation. In contrast to complex 1, the complexes 2-4 induced a dose-dependent formation of reactive oxygen species (ROS), similar to the observed for the reference drugs auranofin and cisplatin. Opposite to 4, complexes 1-3 were able to activate caspase 3/7, suggesting the involvement of apoptosis in the mechanism of cell death. Contrasting with cisplatin, complexes 3, 4 and auranofin did not cause DNA damage. Combined, these data provide evidence that these monoanionic gold bisdithiolates, particularly complex 3, are potential lead compounds to further explore as therapeutic drugs.