2026-04-17T10:26:13Zhttps://riubu.ubu.es/oai/requestoai:riubu.ubu.es:10259/74442026-02-06T12:53:36Zcom_10259_4363com_10259_5086com_10259_2604com_10259_3924com_10259.4_2516com_10259_3592com_10259_3591com_10259.4_106col_10259_4364col_10259_3925col_10259.4_2517col_10259_3930
2023-02-13T11:43:03Z
urn:hdl:10259/7444
Rational design of mitochondria targeted thiabendazole-based Ir(III) biscyclometalated complexes for a multimodal photodynamic therapy of cancer
Echevarría Poza, Igor
Zafon, Elisenda
Barrabés, Sílvia
Martínez, María Ángeles
Ramos Gómez, Sonia
Ortega Santamaría, Natividad
Manzano, Blanca R.
Jalón Sotés, Félix Ángel
Quesada Pato, Roberto
Espino Ordóñez, Gustavo
Massaguer Vall-Llovera, Anna
Photodynamic therapy
Iridium
Cyclometalated complexes
Cancer
Mitochondria
DNA
Despite their outstanding properties as potential photosensitizers for photodynamic therapy (PDT), Ir(III) biscyclometalated complexes need both further developments to overcome remaining limitations and in-depth
investigations into their mechanisms of action to reach clinic application in the treatment of cancer. This
work describes the synthesis of a family of Ir(III) complexes of general formula [Ir(C^N)2(N^N′
)]Cl (N^N′ =
thiabendazole-based ligands; C^N = ppy (2-phenylpyridinate) (Series A), or dfppy (2-(2,4-difluorophenyl)pyridinate) (Series B)) and their evaluation as potential PDT agents. These complexes are partially soluble in water
and exhibit cytotoxic activity in the absence of light irradiation versus several cancer cell lines. Furthermore, the
cytotoxic activity of derivatives of Series A is enhanced upon irradiation, particularly for complexes [1a]Cl and
[3a]Cl, which show phototoxicity indexes (PI) above 20. Endocytosis was established as the uptake mechanism
for [1a]Cl and [3a]Cl in prostate cancer cells by flow cytometry. These derivatives mainly accumulate in the
mitochondria as shown by colocalization confocal microscopy experiments. Presumably, [1a]Cl and [3a]Cl
induce death on cancer cells under irradiation through apoptosis triggered by a multimodal mechanism of action,
which likely involves damage over mitochondrial DNA and mitochondrial membrane depolarization. Both
processes seem to be the result of photocatalytic oxidation processes.
2023-02-13T11:43:03Z
2023-02-13T11:43:03Z
2022-06
info:eu-repo/semantics/article
0162-0134
http://hdl.handle.net/10259/7444
10.1016/j.jinorgbio.2022.111790
eng
Journal of Inorganic Biochemistry. 2022, V. 231, 111790
https://doi.org/10.1016/j.jinorgbio.2022.111790
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-100709-B-C21/ES/NUEVOS METALOFARMACOS DISEÑADOS PARA INCREMENTAR LA SELECTIVIDAD EN TRATAMIENTOS CONTRA EL CANCER. USO DE FOTOTERAPIA Y VEHICULIZACION CON LIGANDOS DIRIGIDOS A TUMORES/
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-100709-B-C22/ES/NUEVOS METALOFARMACOS DISEÑADOS PARA INCREMENTAR LA SELECTIVIDAD. USO DE FOTOTERAPIA Y VEHICULIZACION CON LIGANDOS DIRIGIDOS A TUMORES/
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RED2018-102471-T/ES/METALOFARMACOS MULTIFUNCIONALES PARA DIAGNOSIS Y TERAPIA/
info:eu-repo/grantAgreement/Junta de Castilla y León//BU087G19//Compuestos organometálicos de ir(iii) en terapias antiproliferativas y como sondas químicas deaminas biógenas/
info:eu-repo/grantAgreement/JCCM//SBPLY%2F19%2F180501%2F000260/
info:eu-repo/grantAgreement/UCLM//2019-GRIN-27183/
info:eu-repo/grantAgreement/UCLM//2019-GRIN-27209/
info:eu-repo/grantAgreement/AGAUR//2021 FI_B 01036/
http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
Elsevier