RT info:eu-repo/semantics/article
T1 Targets, Mechanisms and Cytotoxicity of Half-Sandwich Ir(III) Complexes Are Modulated by Structural Modifications on the Benzazole Ancillary Ligand
A1 Acuña, M. Isabel
A1 Rubio Antolin, Ana Rosa
A1 Martínez Alonso, Marta
A1 Busto Vázquez, Natalia
A1 Rodríguez, Ana María
A1 Davila Ferreira, Nerea
A1 Smythe, Carl
A1 Espino Ordóñez, Gustavo
A1 García Ruiz, Begoña
A1 Domínguez, Fernando
K1 Organometallic iridium complex
K1 DNA binding
K1 Mitochondrial damage
K1 Proton leak
K1 Apoptosis
K1 Química física
K1 Chemistry, Physical and theoretical
K1 Fisiología
K1 Physiology
K1 Medicina
K1 Medicine
AB Cancers are driven by multiple genetic mutations but evolve to evade treatments targetingspecific mutations. Nonetheless, cancers cannot evade a treatment that targets mitochondria, whichare essential for tumor progression. Iridium complexes have shown anticancer properties, butthey lack specificity for their intracellular targets, leading to undesirable side effects. Herein wepresent 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 thephysical chemistry properties, cytotoxicity and mechanism of biological action. Neutral complexes,especially those bearing phenylbenzimidazole (HL1 and HL2), restrict the binding to DNA andalbumin. One of them, complex 1[C,NH-Cl], is the most selective one, does not bind DNA, targetsexclusively the mitochondria, disturbs the mitochondria membrane permeability inducing protonleak and increases ROS levels, triggering the molecular machinery of regulated cell death. Inmice with orthotopic lung tumors, the administration of complex 1[C,NH-Cl] reduced the tumorburden. Cancers are more vulnerable than normal tissues to a treatment that harnesses mitochondrialdysfunction. Thus, complex 1[C,NH-Cl] characterization opens the way to the development of newcompounds to exploit this vulnerability
PB MDPI
YR 2022
FD 2022-12
LK http://hdl.handle.net/10259/7561
UL http://hdl.handle.net/10259/7561
LA eng
NO 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.
DS Repositorio Institucional de la Universidad de Burgos
RD 24-abr-2024