doi:10.1021/acs.inorgchem.0c02922engMármol, I.Montanel-Perez, S.Royo, J.C.Gimeno, M.C.Villacampa, M.D.Rodríguez-Yoldi, M.J.Cerrada, E.Gold(I) and Silver(I) Complexes with 2-Anilinopyridine-Based Heterocycles as Multitarget Drugs against Colon CancerART-2020-122422A 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.2020http://zaguan.unizar.es/record/10850510.1021/acs.inorgchem.0c02922http://zaguan.unizar.es/record/108505oai:zaguan.unizar.es:108505info:eu-repo/grantAgreement/ES/DGA/B16-R17info:eu-repo/grantAgreement/ES/DGA-FSE/E07-20Rinfo:eu-repo/grantAgreement/ES/ISCIII-CIBERObn/CB06-03-1012info:eu-repo/grantAgreement/ES/MCIU/RED2018-102471-Tinfo:eu-repo/grantAgreement/ES/MINECO/CTQ2016-75816-C2-1-Pinfo:eu-repo/grantAgreement/ES/MINECO/PID2019-104379RB-C21info:eu-repo/grantAgreement/ES/MINECO/SAF2016-75441-Rinfo:eu-repo/grantAgreement/EUR/SUDOE/INTERREG/Redvalue-SOE1-PI-E0123Inorganic Chemistry 59, 23 (2020), 17732-17745byhttp://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccess