Mechanistic studies on antitumor gold compounds: Decoding protein interactions and proteomic response by mass spectrometry

Gold-based compounds are promising anticancer agents, though their mechanisms are not fully understood. This thesis investigates gold(I) and gold(III) complexes using structural, mass spectrometry, and proteomic approaches. Results show a preferential targeting of protein cysteine residues. In ovarian cancer cells, Auranofin disrupts redox balance and induces ferroptosis, while NHC-based gold(I) complexes trigger ER stress and proteasome inhibition. These results are supported by biochemical validation and further highlight cell-type-dependent effects and differences in cellular uptake. Overall, this work provides a molecular framework for understanding the anticancer activity of gold compounds and demonstrates the value of integrated mass spectrometry and quantitative proteomics in drug mechanism studies.