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

Anna Rovira, Enrique Ortega-Forte, Cormac Hally, Mireia Jordà-Redondo, Diego Abad-Montero, Gloria Vigueras, Jesús I. Martínez, Manel Bosch, Santi Nonell, José Ruiz, Vicente Marchán

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7 Cites (Scopus)

Resum

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.

Idioma originalAnglès
Pàgines (de-a)7849-7867
Nombre de pàgines19
RevistaJournal of Medicinal Chemistry
Volum66
Número12
DOIs
Estat de la publicacióPublicada - 22 de juny 2023

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