2026-04-17T10:28:19Zhttps://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
Echevarría Poza, Igor
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0000-0002-5369-7441
Zafon, Elisenda
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Barrabés, Sílvia
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Martínez, María Ángeles
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Ramos Gómez, Sonia
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500
0000-0001-8056-3900
Ortega Santamaría, Natividad
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Manzano, Blanca R.
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Jalón Sotés, Félix Ángel
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Quesada Pato, Roberto
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0000-0003-2764-7157
Espino Ordóñez, Gustavo
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Massaguer Vall-Llovera, Anna
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2023-02-13T11:43:03Z
2023-02-13T11:43:03Z
2022-06
0162-0134
http://hdl.handle.net/10259/7444
10.1016/j.jinorgbio.2022.111790
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.
We acknowledge the financial support provided by the Spanish Ministerio de Ciencia, Innovacion ´ y Universidades (RTI2018-100709-BC21, RTI2018-100709-B-C22) and CTQ (QMC)-RED2018-102471-T), Junta de Castilla y Leon ´ (BU087G19), Junta de Comunidades de CastillaLa Mancha-FEDER (JCCM) (grant SBPLY/19/180501/000260) and UCLM-FEDER (grants 2019-GRIN-27183 and 2019-GRIN-27209). I. Echevarría wants to acknowledge his fellowship to both the European Social Fund and Consejería de Educacion ´ de la Junta de Castilla y Leon ´ (EDU/1100/2017). E. Zafon wants to acknowledge her predoctoral fellowship to the Generalitat de Catalunya (AGAUR; 2021 FI_B 01036). We are also indebted to Jacinto Delgado, Pilar Castroviejo and Marta Mansilla (PCT of the Universidad de Burgos) for technical support and Jos´e Vicente Cuevas Vicario for advice and support with theoretical calculations and Gabriel García-Herbosa for providing us access to CV equipment.
application/pdf
eng
Elsevier
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/
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
Photodynamic therapy
Iridium
Cyclometalated complexes
Cancer
Mitochondria
DNA
Química orgánica
Química analítica
Química inorgánica
Medicina
Chemistry, Organic
Chemistry, Analytic
Chemistry, Inorganic
Medicine
Rational design of mitochondria targeted thiabendazole-based Ir(III) biscyclometalated complexes for a multimodal photodynamic therapy of cancer
info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
Journal of Inorganic Biochemistry
231
THUMBNAIL
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oai:riubu.ubu.es:10259/7444
2026-02-06 13:53:36.306
Repositorio Institucional de la Universidad de Burgos
bubrep@ubu.es
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