期刊
INORGANIC CHEMISTRY
卷 59, 期 23, 页码 17732-17745出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.inorgchem.0c02922
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资金
- Ministerio de Economiay Competitividad [CTQ2016-75816-C2-1P, PID2019-104379RB-C21, SAF2016-75441-R]
- CIBEROBN of the Instituto Carlos III [CB06/03/1012]
- European Grant Interreg/SUDOE (Redvalue) [SOE1/PI/E0123]
- Red Multimetdrugs [RED2018-102471-T]
- Aragon Regional Government [B16_R17, E07_20R]
A series of gold(I) and silver(I) derivatives with N- or S-donor ligands derived from 2-anilinopyridine has been synthesized and characterized. The mononuclear structure of [Au(L1)(PPh3)](TfO) (1a) and [Au(L2)(PPh3)](TfO) (1b) was confirmed by X-ray diffraction studies, as well as the dinuclear structure in the case of [Ag(TfO)(L1)](2) (4a). Most of the complexes are cytotoxic against a model of colorectal adenocarcinoma (Caco-2 cell line) and breast adenocarcinoma cancer cell lines (MCF-7). [Au(L1)(PPh3)](TfO) (1a) was able to induce caspases 8 and 3 activation, loss of mitochondrial membrane potential, and reactive oxygen species (ROS)-dependent cell death on Caco-2 cells upon 24 h incubation. In addition, the gold complex 1a produced a significant inhibition of the redox enzyme thioredoxin reductase as well as 20S proteasome. However, the silver(I) analogue, [Ag(TfO)(L1)(PPh3)] (2a), induced cell death independent of inhibition of thioredoxin reductase and 20S proteasome, triggered ROS-independent apoptosis mediated by caspase 8 and 3 activation, and loss of mitochondrial membrane potential, which points to a different mechanism of action for both derivatives, dependent on the metal center.
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