NHC-Au-Xanthate Complexes: Selective Cytotoxic Activity and Mechanistic Insights

In this study, a series of NHC-Au-xanthate (NHC-Au-X_a) complexes was evaluated for their antiproliferative activity and mechanism of action. Molecular docking studies identified thioredoxin reductase (TrxR) as a plausible molecular target and suggested that the inhibitory potency may depend on the ability of the complexes to position the gold center in close proximity to the catalytic selenocysteine residue. Consistent with this hypothesis, the investigated compounds induced TrxR inhibition, leading to an intracellular redox imbalance, enhanced reactive oxygen species (ROS) generation, increased release of damage-associated molecular patterns (DAMPs), including HMGB1, and activation of both apoptotic and necrotic cell death pathways. The aforementioned mechanism might indicate the engagement of immunologically relevant cell death responses. Additionally, fluorescence studies demonstrated the preferential accumulation of a representative complex in cancer cells compared with normal fibroblasts. In conclusion, these findings provide new insights into the mechanism of action of NHC-Au-xanthate complexes and highlight their potential as redox-active anticancer agents with possible chemoimmunotherapeutic relevance.