000126601 001__ 126601
000126601 005__ 20241125101149.0
000126601 0247_ $$2doi$$a10.1021/acs.jmedchem.3c00189
000126601 0248_ $$2sideral$$a134101
000126601 037__ $$aART-2023-134101
000126601 041__ $$aeng
000126601 100__ $$aRovira, A.
000126601 245__ $$aExploring structure–activity relationships in photodynamic therapy anticancer agents based on Ir(III)-COUPY conjugates
000126601 260__ $$c2023
000126601 5060_ $$aAccess copy available to the general public$$fUnrestricted
000126601 5203_ $$aPhotodynamic therapy holds great promise as a non-invasive anticancer tool against drug-resistant cancers. However, highly effective, non-toxic, and reliable photosensitizers with operability under hypoxic conditions remain to be developed. Herein, we took the advantageous properties of COUPY fluorophores and cyclometalated Ir(III) complexes to develop novel PDT agents based on Ir(III)-COUPY conjugates with the aim of exploring structure–activity relationships. The structural modifications carried out within the coumarin scaffold had a strong impact on the photophysical properties and cellular uptake of the conjugates. All Ir(III)-COUPY conjugates exhibited high phototoxicity under green light irradiation, which was attributed to the photogeneration of ROS, while remaining non-toxic in the dark. Among them, two hit conjugates showed excellent phototherapeutic indexes in cisplatin-resistant A2780cis cancer cells, both in normoxia and in hypoxia, suggesting that photoactive therapy approaches based on the conjugation of far-red/NIR-emitting COUPY dyes and transition metal complexes could effectively tackle in vitro acquired resistance to cisplatin.
000126601 536__ $$9info:eu-repo/grantAgreement/ES/MICINN/CTQ2016-78454-C2-1-R$$9info:eu-repo/grantAgreement/ES/MICINN/CTQ2017-84779-R$$9info:eu-repo/grantAgreement/ES/MICINN/PID2020-115801RB-C22$$9info:eu-repo/grantAgreement/ES/MICINN/PID2020-117508RB-I00$$9info:eu-repo/grantAgreement/ES/MICINN/PID2021-122850NB-I00$$9info:eu-repo/grantAgreement/ES/MICINN/RTI2018-096891-B-I00
000126601 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000126601 590__ $$a6.9$$b2023
000126601 592__ $$a1.986$$b2023
000126601 591__ $$aCHEMISTRY, MEDICINAL$$b3 / 72 = 0.042$$c2023$$dQ1$$eT1
000126601 593__ $$aMolecular Medicine$$c2023$$dQ1
000126601 593__ $$aDrug Discovery$$c2023$$dQ1
000126601 594__ $$a12.8$$b2023
000126601 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000126601 700__ $$aOrtega-Forte, E.
000126601 700__ $$aHally, C.
000126601 700__ $$aJordà-Redondo, M.
000126601 700__ $$aAbad-Montero, D.
000126601 700__ $$aVigueras, G.
000126601 700__ $$0(orcid)0000-0002-5406-3280$$aMartínez, J. I.$$uUniversidad de Zaragoza
000126601 700__ $$aBosch, M.
000126601 700__ $$aNonell, S.
000126601 700__ $$aRuiz, J.
000126601 700__ $$aMarchán, V.
000126601 7102_ $$12003$$2395$$aUniversidad de Zaragoza$$bDpto. Física Materia Condensa.$$cÁrea Física Materia Condensada
000126601 773__ $$g66, 12 (2023), 7849-7867$$pJ. med. chem.$$tJournal of medicinal chemistry$$x0022-2623
000126601 8564_ $$s3892500$$uhttps://zaguan.unizar.es/record/126601/files/texto_completo.pdf$$yVersión publicada
000126601 8564_ $$s3098107$$uhttps://zaguan.unizar.es/record/126601/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000126601 909CO $$ooai:zaguan.unizar.es:126601$$particulos$$pdriver
000126601 951__ $$a2024-11-22-12:05:47
000126601 980__ $$aARTICLE