2024-03-29T09:02:12Zhttps://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
Acuña, M. Isabel
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600
Rubio Antolin, Ana Rosa
491
600
0000-0002-8504-9692
Martínez Alonso, Marta
772
600
0000-0002-0931-5274
Busto Vázquez, Natalia
83
600
0000-0001-9637-1209
Rodríguez, Ana María
acb36428-a2da-4e1b-a8d8-1f616e7c00b5
600
Davila Ferreira, Nerea
838e64a3-dde1-4b34-b260-e0fd35b70b36
600
Smythe, Carl
b78e6582-65fe-4307-b274-dfe4143fa992
600
Espino Ordóñez, Gustavo
162
600
0000-0001-5617-5705
García Ruiz, Begoña
217
600
0000-0002-0817-1651
Domínguez, Fernando
b2bd4d22-043f-4d2e-b221-825845d10230
600
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
We acknowledge the “la Caixa” Foundation (LCF/PR/PR12/11070003), Ministerio de Ciencia Innovación y Universidades-FEDER (RTI2018-102040-B-100) and Junta de Castilla y León-FEDER (BU305P18) for financial support. Networking support by COST Action CA18202 (NECTAR) is also acknowledged.
application/pdf
eng
MDPI
Cancers. 2022, V. 15, n. 1, 107
https://doi.org/10.3390/cancers15010107
info:eu-repo/grantAgreement/Fundación Bancaria Caixa d'Estalvis i Pensions de Barcelona//LCF%2FPR%2FPR12%2F11070003//
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-102040-B-I00/ES/PROPIEDADES ANTIMICROBIANAS DE NUEVOS COMPLEJOS ORGANOMETALICOS/
info:eu-repo/grantAgreement/Junta de Castilla y León//BU305P18//DISEÑO Y CARACTERIZACIÓN DE COMPLEJOS BIOINORGÁNICOS Y CLÚSTERES CUÁNTICOS ATÓMICOS. PROPIEDADES ANTIMICROBIANAS EN CEPAS RESISTENTES. PROPIEDADES ANTITUMORALES EN LA OSCURIDAD Y BAJO IRRADIACIÓN/
info:eu-repo/grantAgreement/COST//CA18202/EU/Network for Equilibria and Chemical Thermodynamics Advanced Research/NECTAR/
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
Organometallic iridium complex
DNA binding
Mitochondrial damage
Proton leak
Apoptosis
Química física
Physiology
Chemistry, Physical and theoretical
Fisiología
Medicina
Medicine
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
info:eu-repo/semantics/publishedVersion
Cancers
15
1
THUMBNAIL
Acuña-Cancers_2022.pdf.jpg
Acuña-Cancers_2022.pdf.jpg
IM Thumbnail
image/jpeg
3393
https://riubu.ubu.es/bitstream/10259/7561/4/Acu%c3%b1a-Cancers_2022.pdf.jpg
f163b84775a604e32c157ab2d65f466d
MD5
4
LICENSE
license.txt
license.txt
text/plain; charset=utf-8
1362
https://riubu.ubu.es/bitstream/10259/7561/3/license.txt
5d013bfa6e473ff0db22cd82a4d71a70
MD5
3
CC-LICENSE
license_rdf
license_rdf
application/rdf+xml; charset=utf-8
908
https://riubu.ubu.es/bitstream/10259/7561/2/license_rdf
0175ea4a2d4caec4bbcc37e300941108
MD5
2
ORIGINAL
Acuña-Cancers_2022.pdf
Acuña-Cancers_2022.pdf
application/pdf
3779876
https://riubu.ubu.es/bitstream/10259/7561/1/Acu%c3%b1a-Cancers_2022.pdf
1a36ad7b4171bf0497fb8498219712ea
MD5
1
10259/7561
oai:riubu.ubu.es:10259/7561
2023-04-19 10:00:45.901
Repositorio Institucional de la Universidad de Burgos
bubrep@ubu.es
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