Exploring structure–activity relationships in photodynamic therapy anticancer agents based on Ir(III)-COUPY conjugates

Rovira, A. ; Ortega-Forte, E. ; Hally, C. ; Jordà-Redondo, M. ; Abad-Montero, D. ; Vigueras, G. ; Martínez, J. I. (Universidad de Zaragoza) ; Bosch, M. ; Nonell, S. ; Ruiz, J. ; Marchán, V.

Resumen: 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: Inglés

DOI: 10.1021/acs.jmedchem.3c00189

Año: 2023

Publicado en: Journal of medicinal chemistry 66, 12 (2023), 7849-7867
ISSN: 0022-2623

Factor impacto JCR: 6.9 (2023)

Categ. JCR: CHEMISTRY, MEDICINAL rank: 3 / 72 = 0.042 (2023) - Q1 - T1

Factor impacto CITESCORE: 12.8 - Drug Discovery (Q1) - Molecular Medicine (Q1)

Factor impacto SCIMAGO: 1.986 - Molecular Medicine (Q1) - Drug Discovery (Q1)

Financiación: info:eu-repo/grantAgreement/ES/MICINN/CTQ2016-78454-C2-1-R
Financiación: info:eu-repo/grantAgreement/ES/MICINN/CTQ2017-84779-R
Financiación: info:eu-repo/grantAgreement/ES/MICINN/PID2020-115801RB-C22
Financiación: info:eu-repo/grantAgreement/ES/MICINN/PID2020-117508RB-I00
Financiación: info:eu-repo/grantAgreement/ES/MICINN/PID2021-122850NB-I00
Financiación: info:eu-repo/grantAgreement/ES/MICINN/RTI2018-096891-B-I00

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Física Materia Condensada (Dpto. Física Materia Condensa.)