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cc-by (c) Rovira, Anna , 2023
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/201842

Exploring Structure-Activity Relationships in Photodynamic Therapy Anticancer Agents Based on Ir(III)-COUPY Conjugates

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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.

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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. Exploring Structure-Activity Relationships in Photodynamic Therapy Anticancer Agents Based on Ir(III)-COUPY Conjugates. _Journal of Medicinal Chemistry_. 2023. Vol. 66, núm. 12, pàgs. 7849-7867. [consulta: 12 de abril de 2026]. ISSN: 0022-2623. [Disponible a: https://hdl.handle.net/2445/201842]

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