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oai:recercat.cat:2445/2018422025-12-04T21:45:27Zcom_2072_1057col_2072_478917col_2072_478933

Exploring Structure-Activity Relationships in Photodynamic Therapy Anticancer Agents Based on Ir(III)-COUPY Conjugates Rovira, Anna Ortega Forte, Enrique Hally, Cormac Jordà-Redondo, Mireia Abad-Montero, Diego Vigueras, Gloria Martínez, Jesús I. Bosch Marimon, Manel Nonell, Santi Ruiz, José Marchán Sancho, Vicente Compostos aromàtics Cèl·lules canceroses Cumarines Aromatic compounds Cancer cells Coumarins Photodynamic 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. 2023-09-08T15:51:44Z 2023-09-08T15:51:44Z 2023-06-02 2023-09-08T15:51:44Z info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion 0022-2623 https://hdl.handle.net/2445/201842 738222 eng Reproducció del document publicat a: https://doi.org/10.1021/acs.jmedchem.3c00189 Journal of Medicinal Chemistry, 2023, vol. 66, num. 12, p. 7849-7867 https://doi.org/10.1021/acs.jmedchem.3c00189 cc-by (c) Rovira, Anna , 2023 http://creativecommons.org/licenses/by/3.0/es/ info:eu-repo/semantics/openAccess 19 p. application/pdf American Chemical Society Articles publicats en revistes (Química Inorgànica i Orgànica)