2024-03-28T19:26:31Zhttps://riubu.ubu.es/oai/requestoai:riubu.ubu.es:10259/75612023-04-19T08:00:45Zcom_10259_4365com_10259_5086com_10259_2604com_10259_4363com_10259_6185com_10259_3591com_10259.4_106col_10259_4366col_10259_4364col_10259_6186
Repositorio Institucional de la Universidad de Burgos
author
Acuña, M. Isabel
author
Rubio Antolin, Ana Rosa
author
Martínez Alonso, Marta
author
Busto Vázquez, Natalia
author
Rodríguez, Ana María
author
Davila Ferreira, Nerea
author
Smythe, Carl
author
Espino Ordóñez, Gustavo
author
García Ruiz, Begoña
author
Domínguez, Fernando
2023-03-20T10:47:17Z
2023-03-20T10:47:17Z
2022-12
http://hdl.handle.net/10259/7561
10.3390/cancers15010107
2072-6694
Cancers are driven by multiple genetic mutations but evolve to evade treatments targeting
specific mutations. Nonetheless, cancers cannot evade a treatment that targets mitochondria, which
are essential for tumor progression. Iridium complexes have shown anticancer properties, but
they lack specificity for their intracellular targets, leading to undesirable side effects. Herein we
present a systematic study on structure-activity relationships of eight arylbenzazole-based Iridium(III)
complexes of type [IrCl(Cp*)], that have revealed the role of each atom of the ancillary ligand in the
physical chemistry properties, cytotoxicity and mechanism of biological action. Neutral complexes,
especially those bearing phenylbenzimidazole (HL1 and HL2), restrict the binding to DNA and
albumin. One of them, complex 1[C,NH-Cl], is the most selective one, does not bind DNA, targets
exclusively the mitochondria, disturbs the mitochondria membrane permeability inducing proton
leak and increases ROS levels, triggering the molecular machinery of regulated cell death. In
mice with orthotopic lung tumors, the administration of complex 1[C,NH-Cl] reduced the tumor
burden. Cancers are more vulnerable than normal tissues to a treatment that harnesses mitochondrial
dysfunction. Thus, complex 1[C,NH-Cl] characterization opens the way to the development of new
compounds to exploit this vulnerability
eng
Atribución 4.0 Internacional
Organometallic iridium complex
DNA binding
Mitochondrial damage
Proton leak
Apoptosis
Targets, Mechanisms and Cytotoxicity of Half-Sandwich Ir(III) Complexes Are Modulated by Structural Modifications on the Benzazole Ancillary Ligand
info:eu-repo/semantics/article
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URL
https://riubu.ubu.es/bitstream/10259/7561/1/Acu%c3%b1a-Cancers_2022.pdf
File
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3779876
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Acuña-Cancers_2022.pdf