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Los ligandos de bidentato en los complejos de nitrido de osmio (VI) controlan la orientación intracelular y las vías
Kogularamanan Suntharalingam1, Timothy C Johnstone, Peter M Bruno
1Department of Chemistry, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
Journal of the American Chemical Society
|September 18, 2013
Resumen
Los compuestos de osmio antiproliferantes muestran respuestas celulares sintonizables. La modificación de ligandos en el complejo 4 induce estrés en el retículo endoplasmático y apoptosis independiente de p53 en las células cancerosas.
Área de la Ciencia:
- Química Inorgánica La Química Inorgánica es la química inorgánica.
- Biología del cáncer Biología del cáncer.
- Respuesta Celular al Estrés Respuesta Celular al Estrés
Sus antecedentes:
- Los compuestos de nitruro de osmio (OsN) antiproliferantes (OsN) se investigan para la terapia del cáncer.
- Las modificaciones de ligandos en estos complejos de osmio pueden alterar su actividad biológica.
Objetivo del estudio:
- Para investigar la respuesta celular de los compuestos de nitruro de osmio (VI) con diferentes ligandos.
- Comprender el mecanismo de acción de los compuestos de osmio en las células cancerosas.
Principales métodos:
- Síntesis y caracterización de compuestos de nitruro de osmio (VI) con diferentes ligandos N^N.
- Pruebas celulares para evaluar el daño del ADN, la progresión del ciclo celular y la apoptosis.
- Análisis de la expresión proteica relacionada con la vía p53 y la respuesta proteica desplegada.
Principales resultados:
- El daño del ADN inducido por el complejo 2, la activación de la vía p53, la detención del ciclo celular G2 / M y la apoptosis dependiente de la caspasa.
- El complejo 4 indujo estrés en el retículo endoplasmático (ER), activación de la vía de respuesta proteica desplegada (UPR) y apoptosis independiente de p53.
- El Compuesto 4 es el primer compuesto de osmio reportado para inducir estrés ER en células cancerosas.
Conclusiones:
- Las sutiles modificaciones de ligandos en los compuestos de nitruro de osmio (VI) pueden ajustar con precisión las respuestas celulares.
- El complejo de osmio 4 representa una nueva estrategia terapéutica mediante la inducción de la apoptosis mediada por el estrés ER.
- Se justifica una mayor investigación sobre los compuestos a base de osmio para el tratamiento del cáncer.
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