171652 20260527123126.0 doi 10.1021/acs.inorgchem.5c05908 sideral 149355 ART-2026-149355 eng Sáez, Javier Dual-Action NSAID-Gold(I) Alkynyl Hybrids for Synergistic Anti-Inflammatory and Anticancer Therapy of Colorectal Cancer 2026 Colorectal cancer (CRC) remains a major global health challenge, in which chronic inflammation and redox dysregulation are key drivers of tumor progression. Here, we report a rationally designed family of NSAID-derived alkyne ligands coordinated to JohnPhos–gold(I) fragments, affording eight new alkynyl gold(I) derivatives. Complexes based on naproxen, ibuprofen, and salicylic acid derivatives display potent antiproliferative activity against Caco-2/TC7 colon cancer cells, outperforming oxaliplatin and being comparable to auranofin, while showing markedly reduced cytotoxicity in breast cancer lines and nonmalignant cells, thus indicating promising selectivity. Mechanistic studies revealed that the most active complex, [Au(L1)JP] (1), which contains a naproxen-derived alkyne, inhibits thioredoxin reductase (TrxR), triggers ROS overproduction, disrupts mitochondrial membrane potential, and induces G1-phase arrest while only marginally increasing apoptosis. This suggests the involvement of additional forms of cell death or cytostatic effects. Additionally, complex 1 selectively inhibits the enzyme cyclooxygenase-2 (COX-2) over COX-1 and reduces IL-8 expression without affecting PTGS2 transcription, highlighting a post-transcriptional anti-inflammatory action. These results support NSAID-derived alkynyl gold(I) complexes as promising multitarget agents for colorectal cancer intervention, combining disruption and COX-2 modulation. Access copy available to the general public Unrestricted info:eu-repo/grantAgreement/ES/CIBERObn/CB06-03-1012 info:eu-repo/grantAgreement/ES/DGA/B16-23R info:eu-repo/grantAgreement/ES/DGA/E07-23R info:eu-repo/grantAgreement/ES/MICIU AEI/PID2022-136861NB-I00 info:eu-repo/semantics/openAccess by https://creativecommons.org/licenses/by/4.0/deed.es info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Herrera-Marcos, Luis Vicente Universidad de Zaragoza (orcid)0000-0002-4665-9674 Rodríguez-Yoldi, María Jesús Universidad de Zaragoza (orcid)0000-0002-3595-7668 Gimeno, M. Concepción (orcid)0000-0003-0553-0695 Cerrada, Elena Universidad de Zaragoza (orcid)0000-0003-2457-3674 2010 760 Universidad de Zaragoza Dpto. Química Inorgánica Área Química Inorgánica 1012 410 Universidad de Zaragoza Dpto. Farmac.Fisiol.y Med.L.F. Área Fisiología 1012 315 Universidad de Zaragoza Dpto. Farmac.Fisiol.y Med.L.F. Área Farmacología 65, 13 (2026), 7210-7223 Inorg. chem. Inorganic Chemistry 0020-1669 6919741 http://zaguan.unizar.es/record/171652/files/texto_completo.pdf Versión publicada 3218089 http://zaguan.unizar.es/record/171652/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:171652 articulos driver 2026-05-27-11:25:49 ARTICLE