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J Biol Inorg Chem ; 13(6): 861-71, 2008 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-18418632

RESUMEN

The development of complexes that allow the monitoring of the release and distribution of fluorescent models of anticancer drugs initially bound to cobalt(III) moieties is reported. Strong quenching of fluorescence upon ligation to cobalt(III) was observed for both the carboxylate- and the hydroximate-bound fluorophores as was the partial return of fluorescence following addition of ascorbate and cysteine. The extent of the increase in the fluorescence intensity observed following addition of these potential reductants is indicative of the fluorophore being displaced from the complex by the action of ascorbate or cysteine, by ligand exchange. The cellular distribution of the fluorescence revealed that coordination to cobalt can dramatically alter the subcellular distribution of a bound fluorophore. This work shows that fluorescence can be an effective means of monitoring these agents in cells, and of determining their sites of activation. The results also reveal that the cytotoxicity of such agents correlates with their uptake and distribution patterns and that these are influenced by the types of ligands attached to the complex.


Asunto(s)
Colorantes Fluorescentes/farmacocinética , Compuestos Organometálicos/farmacocinética , Ácido Ascórbico/química , Sitios de Unión , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Cobalto/química , Cisteína/química , Ensayos de Selección de Medicamentos Antitumorales , Electroquímica , Colorantes Fluorescentes/síntesis química , Colorantes Fluorescentes/química , Humanos , Ligandos , Microscopía Confocal , Conformación Molecular , Compuestos Organometálicos/síntesis química , Compuestos Organometálicos/química , Oxidación-Reducción , Estereoisomerismo , Factores de Tiempo , Distribución Tisular
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