000171652 001__ 171652
000171652 005__ 20260527123126.0
000171652 0247_ $$2doi$$a10.1021/acs.inorgchem.5c05908
000171652 0248_ $$2sideral$$a149355
000171652 037__ $$aART-2026-149355
000171652 041__ $$aeng
000171652 100__ $$aSáez, Javier
000171652 245__ $$aDual-Action NSAID-Gold(I) Alkynyl Hybrids for Synergistic Anti-Inflammatory and Anticancer Therapy of Colorectal Cancer
000171652 260__ $$c2026
000171652 5060_ $$aAccess copy available to the general public$$fUnrestricted
000171652 5203_ $$aColorectal 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.
000171652 536__ $$9info:eu-repo/grantAgreement/ES/CIBERObn/CB06-03-1012$$9info:eu-repo/grantAgreement/ES/DGA/B16-23R$$9info:eu-repo/grantAgreement/ES/DGA/E07-23R$$9info:eu-repo/grantAgreement/ES/MICIU AEI/PID2022-136861NB-I00
000171652 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttps://creativecommons.org/licenses/by/4.0/deed.es
000171652 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000171652 700__ $$0(orcid)0000-0002-4665-9674$$aHerrera-Marcos, Luis Vicente$$uUniversidad de Zaragoza
000171652 700__ $$0(orcid)0000-0002-3595-7668$$aRodríguez-Yoldi, María Jesús$$uUniversidad de Zaragoza
000171652 700__ $$0(orcid)0000-0003-0553-0695$$aGimeno, M. Concepción
000171652 700__ $$0(orcid)0000-0003-2457-3674$$aCerrada, Elena$$uUniversidad de Zaragoza
000171652 7102_ $$12010$$2760$$aUniversidad de Zaragoza$$bDpto. Química Inorgánica$$cÁrea Química Inorgánica
000171652 7102_ $$11012$$2410$$aUniversidad de Zaragoza$$bDpto. Farmac.Fisiol.y Med.L.F.$$cÁrea Fisiología
000171652 7102_ $$11012$$2315$$aUniversidad de Zaragoza$$bDpto. Farmac.Fisiol.y Med.L.F.$$cÁrea Farmacología
000171652 773__ $$g65, 13 (2026), 7210-7223$$pInorg. chem.$$tInorganic Chemistry$$x0020-1669
000171652 8564_ $$s6919741$$uhttps://zaguan.unizar.es/record/171652/files/texto_completo.pdf$$yVersión publicada
000171652 8564_ $$s3218089$$uhttps://zaguan.unizar.es/record/171652/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000171652 909CO $$ooai:zaguan.unizar.es:171652$$particulos$$pdriver
000171652 951__ $$a2026-05-27-11:25:49
000171652 980__ $$aARTICLE