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Peer-reviewedCC BY 4.0ACS Omega

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

  • Katarzyna Niemirowicz-Laskowska1
  • Marta Pietruszyńska2
  • Supratim Chakraborty3
  • Piotr F. J. Lipiński4
  • Wioletta Kośnik5
  • Beata Skonieczna1
  • Iwona Misztalewska-Turkowicz6
  • Halina Car1,2
  • Michał Michalak3
6 affiliations
  1. 1Medical University of Białystok , , Szpitalna 37 , ,
  2. 2Medical University of Bialystok , , Waszyngtona 15A , ,
  3. 3Polish Academy of Sciences , , Kasprzaka 44/52 , ,
  4. 4Polish Academy of Sciences , , Pawinskiego 5 , ,
  5. 5NanoVelos S.A. , Rakowiecka 36 , ,
  6. 6University of Bialystok , , Ciolkowskiego 1K , ,
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Abstract

In this study, a series of NHC-Au-xanthate (NHC-Au-Xa) 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.

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Cite

BibTeXRIS
BibTeX
@article{niemirowiczlaskowska2026nhcauxanthate,
  title = {{NHC-Au-Xanthate Complexes: Selective Cytotoxic Activity and Mechanistic Insights}},
  author = {Katarzyna Niemirowicz-Laskowska and Marta Pietruszyńska and Supratim Chakraborty and Piotr F. J. Lipiński and Wioletta Kośnik and Beata Skonieczna and Iwona Misztalewska-Turkowicz and Halina Car and Michał Michalak},
  journal = {ACS Omega},
  year = {2026},
  month = oct,
  doi = {10.1021/acsomega.6c07778},
  url = {https://pubs.acs.org/acsodf/article/11/42/65351/5449269/NHC-Au-Xanthate-Complexes-Selective-Cytotoxic},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - NHC-Au-Xanthate Complexes: Selective Cytotoxic Activity and Mechanistic Insights
AU  - Katarzyna Niemirowicz-Laskowska
AU  - Marta Pietruszyńska
AU  - Supratim Chakraborty
AU  - Piotr F. J. Lipiński
AU  - Wioletta Kośnik
AU  - Beata Skonieczna
AU  - Iwona Misztalewska-Turkowicz
AU  - Halina Car
AU  - Michał Michalak
PY  - 2026
DA  - 2026/10/12
JO  - ACS Omega
DO  - 10.1021/acsomega.6c07778
UR  - https://pubs.acs.org/acsodf/article/11/42/65351/5449269/NHC-Au-Xanthate-Complexes-Selective-Cytotoxic
AB  - In this study, a series of NHC-Au-xanthate (NHC-Au-Xa) 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.
SN  - 2470-1343
ER  -