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Síntesis total de la lisobactina
Aikomari Guzman-Martinez1, Ryan Lamer, Michael S VanNieuwenhze
1Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, California 92093, USA.
Journal of the American Chemical Society
|April 17, 2007
Resumen
La lisobactina, un nuevo antibiótico, muestra una potente actividad contra bacterias resistentes como MRSA y VRE. Su mecanismo único de inhibir la formación de peptidoglicano ofrece una nueva estrategia de tratamiento prometedora para las infecciones difíciles.
Área de la Ciencia:
- Microbiología Microbiología.
- Química Medicinal La Química Medicinal es el campo de la Química Medicinal.
- Descubrimiento de Drogas Descubrimiento de Drogas
Sus antecedentes:
- La resistencia a los antibióticos es una gran amenaza para la salud mundial, lo que hace necesario el desarrollo de nuevos medicamentos con nuevos mecanismos de acción.
- Los antibióticos existentes son cada vez menos eficaces contra las cepas bacterianas multirresistentes.
- La lisobactina es un antibiótico depsipeptido con actividad potente demostrada contra patógenos resistentes.
Objetivo del estudio:
- Para evaluar la actividad antibacteriana de la lisobactina contra las cepas bacterianas resistentes.
- Para investigar el mecanismo de acción de la lisobactina.
- Desarrollar una vía sintética para la lisobactina y sus análogos.
Principales métodos:
- Se realizaron ensayos de concentración inhibidora mínima (MIC) contra el Staphylococcus aureus resistente a la meticilina (MRSA) y los enterococos resistentes a la vancomicina (VRE).
- Se evaluó el efecto de la lisobactina en la formación de peptidoglicanos.
- Se empleó una estrategia de síntesis convergente que involucra la macrociclación para producir lisobactina.
Principales resultados:
- La lisobactina exhibió una fuerte actividad antibacteriana contra el SARM y el ERV, con ICM que oscilaron entre 0,39 y 0,78 microg / ml.
- Contra la ERV, los CMI de la lisobactina fueron más de 50 veces más bajos que los de la vancomicina.
- La lisobactina inhibió la formación naciente de peptidoglicano a través de un mecanismo distinto al de la vancomicina.
Conclusiones:
- La lisobactina es un candidato prometedor para el tratamiento de infecciones causadas por bacterias resistentes a los antibióticos.
- El mecanismo de acción distinto y la actividad potente hacen que la lisobactina sea valiosa para futuras investigaciones.
- La síntesis desarrollada proporciona una base para crear y estudiar análogos de lisobactina.
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