| Affiliation: | 1. Department of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093 USA Department of Chemistry, Department of Materials Science & Engineering, Department of Biomedical Engineering and Department of Pharmacology, International Institute for Nanotechnology, Simpson Querrey Institute, Chemistry of Life Processes Institute and Lurie Cancer Center, Northwestern University, Evanston, Il, 60208 USA;2. Department of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093 USA;3. UCSD-CNRS Joint Research Laboratory (UMI 3555), Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, 92093-0358 USA |
| Abstract: | Cyclic (Alkyl)(Amino)Carbenes (CAACs) have become forceful ligands for gold due to their ability to form very strong ligand-metal bonds. Inspired by the success of Auranofin and other gold complexes as antitumor agents, we have studied the cytotoxicity of bis- and mono-CAAC-gold complexes on different cancer cell lines: HeLa (cervical cancer), A549 (lung cancer), HT1080 (fibrosarcoma) and Caov-3 (ovarian cancer). Further investigations aimed at elucidating their mechanism of action are described. This includes quantification of affinities for TrxR, evaluation of their bioavailability and determination of associated cell death process. Moreover, Transmission Electron Microscopy (TEM) was used to study morphological changes upon exposure. Noticeably, a significant reduction in non-specific binding to serum proteins was observed with CAAC complexes when compared to Auranofin. These results confirm the potential of CAAC-gold complexes in biological environments, which may result in more specific drug-target interactions and decreased side effects. |
