Organoiridium Photosensitizers Induce Specific Oxidative Attack on Proteins within Cancer Cells.
Angew Chem Int Ed Engl
; 56(47): 14898-14902, 2017 11 20.
Article
em En
| MEDLINE
| ID: mdl-29047228
ABSTRACT
Strongly luminescent iridium(III) complexes, [Ir(C,N)2 (S,S)]+ (1) and [Ir(C,N)2 (O,O)] (2), containing C,N (phenylquinoline), O,O (diketonate), or S,S (dithione) chelating ligands, have been characterized by X-ray crystallography and DFT calculations. Their long phosphorescence lifetimes in living cancer cells give rise to high quantum yields for the generation of 1 O2 , with large 2-photon absorption cross-sections. 2 is nontoxic to cells, but potently cytotoxic to cancer cells upon brief irradiation with low doses of visible light, and potent at sub-micromolar doses towards 3D multicellular tumor spheroids with 2-photon red light. Photoactivation causes oxidative damage to specific histidine residues in the key proteins in aldose reductase and heat-shock protein-70 within living cancer cells. The oxidative stress induced by iridium photosensitizers during photoactivation can increase the levels of enzymes involved in the glycolytic pathway.
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Base de dados:
MEDLINE
Assunto principal:
Compostos Organometálicos
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Quinolinas
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Fármacos Fotossensibilizantes
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Irídio
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Proteínas de Neoplasias
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article