Gold(I) and Silver(I) Complexes with 2-Anilinopyridine-Based Heterocycles as Multitarget Drugs against Colon Cancer.

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)(PPh) () and Au(L2)(PPh) () was confirmed by X-ray diffraction studies, as well as the dinuclear structure in the case of [Ag(TfO)(L1)] (). 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)(PPh) () 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 produced a significant inhibition of the redox enzyme thioredoxin reductase as well as 20S proteasome. However, the silver(I) analogue, [Ag(TfO)(L1)(PPh)] (), 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.