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Actividad de inducción de la apoptosis mediada por cloruro de los anionoforos de bis (sulfonamida)
Tanmoy Saha1, Munshi Sahid Hossain1, Debasis Saha1
1Department of Chemistry, Indian Institute of Science Education and Research Pune , Pune, Maharashtra 411008, India.
Journal of the American Chemical Society
|May 26, 2016
Resumen
Las bis ((sulfonamidas) transportan eficientemente los iones cloruro a través de las membranas celulares, alterando el equilibrio iónico e induciendo la muerte de las células cancerosas a través de la apoptosis. Esto pone de relieve su potencial en la terapia contra el cáncer al dirigirse al transporte de aniones transmembrana.
Área de la Ciencia:
- Química supramolecular
- Transporte por membrana
- Terapia contra el cáncer
Sus antecedentes:
- El transporte de aniones transmembrana es crucial para la función celular y un objetivo para las terapias contra el cáncer.
- El desarrollo de receptores de aniones eficientes y selectivos es clave para avanzar en este campo.
Objetivo del estudio:
- Investigar las bis (sulfonamidas) como nuevos receptores para la unión y el transporte selectivo de iones cloruro.
- Explorar el mecanismo del transporte de iones y su efecto sobre la viabilidad de las células cancerosas.
Principales métodos:
- Resonancia magnética nuclear de protones ((1) H NMR) para estudios de unión de aniones.
- Evaluación de la lipofilidad de las moléculas receptoras.
- Ensayos fluorescentes para la determinación del mecanismo de transporte de iones.
- Potencial de membrana mitocondrial, fuga de citocromo c, activación de la caspasa y análisis de fragmentación nuclear para confirmar la apoptosis.
Principales resultados:
- Las bis ((sulfonamidas) exhiben una fuerte y selectiva unión de iones cloruro, correlacionada con la acidez del protón N-H de la sulfonamida.
- La lipofilia influye significativamente en la eficiencia del transporte de iones.
- Las amidas bis (sulfonamidas) muestran una mayor actividad de unión y transporte de aniones en comparación con las amidas bis (carboxílicas).
- El transporte de iones cloruro por bis ((sulfonamidas) funciona a través de un mecanismo antipuerto Cl ((-) / anión, lo que lleva a la interrupción de la homeostasis iónica y la muerte celular a través de la apoptosis.
Conclusiones:
- Las bis ((sulfonamidas) son receptores efectivos para el transporte de iones cloruro transmembrana.
- La interrupción de la homeostasis iónica celular por el transporte de cloruro mediado por bis (sulfonamida) induce la apoptosis en las células cancerosas.
- Estos hallazgos presentan las bis ((sulfonamidas) como candidatos prometedores para el desarrollo de nuevos agentes anticancerígenos dirigidos al transporte de aniones.
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