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Ajuste de la reactividad de los complejos de osmio (II) y rutenio (II) areno bajo condiciones fisiológicas

Anna F A Peacock¹, Abraha Habtemariam, Rafael Fernández

¹Contribution from the School of Chemistry, University of Edinburgh, West Mains Road, Edinburgh EH9 3JJ, U.K.

Journal of the American Chemical Society

|February 2, 2006

Resumen

Los complejos de osmio (II) areno con ligandos de etilendiamina muestran inactividad hacia las células de cáncer de ovario. La sustitución de etilenediamina por acetilacetonato conduce a una hidrólisis rápida y la formación de dímeros inactivos, haciéndolos ineficaces contra las células de cáncer de pulmón.

Área de la Ciencia:

Química organometálica Química orgánica de los metales.
Química Inorgánica Medicinal Química Inorgánica para uso medicinal
Terapéutica del cáncer Terapéutica del cáncer.

Sus antecedentes:

Los complejos de rutenio (II) y osmio (II) areno se investigan para las propiedades anticancerígenas.
Los ligandos etilendiamina (en) y acetilacetonato (acac) influyen en la reactividad y actividad biológica de estos complejos metálicos.
La hidrólisis y la unión a las nucleobases son factores críticos que determinan la eficacia de los agentes anticancerígenos a base de metales.

Objetivo del estudio:

Para evaluar la actividad anticancerígena de los complejos de Os(II) areno con diferentes ligandos quelantes (en vs. acac).
Para investigar el comportamiento de hidrólisis y la reactividad de las nucleobases de estos complejos Os (II).
Comprender cómo la elección de ligandos impacta el potencial de los complejos de arenos Os (II) y Ru (II) como agentes anticancerígenos.

Principales métodos:

Síntesis y caracterización de los complejos de Os(II) areno con etilendiamina y los ligandos de acetilacetonato.
Ensayos de citotoxicidad in vitro contra las líneas celulares de cáncer de pulmón A2780 y A549 del ovario.
Estudios de la velocidad de hidrólisis, determinación de pKa de los aductos de agua y cinética de reacción con las nucleobases (9-etilguanina, adenosina, citidina, timidina).

Principales resultados:

Los complejos de Os(II) arenoetilendiamina eran inactivos contra las células de cáncer de ovario.
Los complejos de acetilacetonato de Os(II) areno se sometieron a una rápida hidrólisis, formando dímeros inactivos con puente hidroxo a pH fisiológico.
A pesar de la reactividad con algunas nucleobases, los complejos de acetilacetonato no mostraron actividad contra las células de cáncer de pulmón debido a la formación de dímeros.

Conclusiones:

El ligando quelante tiene un impacto significativo en la hidrólisis y en la unión de nucleobases de los complejos de Os(II) areno.
La hidrólisis rápida y la formación de dímeros no reactivos limitan el potencial anticancerígeno de los complejos de acetilacetonato de Os(II) areno.
El diseño de los ligandos es crucial para ajustar la reactividad y desarrollar fármacos anticancerígenos eficaces basados en metales.

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