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Una plataforma para el descubrimiento de nuevos antibióticos macrólidos
Ian B Seiple1, Ziyang Zhang1, Pavol Jakubec1
1Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Nature
|May 20, 2016
Resumen
Una nueva vía totalmente sintética permite la creación de nuevos candidatos a antibióticos macrólidos, incluida la solitromicina. Este enfoque supera la resistencia bacteriana y ofrece una plataforma para el descubrimiento y la fabricación de nuevos antibióticos.
Área de la Ciencia:
- Química orgánica
- Química medicinal
- Microbiología
Sus antecedentes:
- La semisíntesis de productos complejos de fermentación es crucial para el descubrimiento de antibióticos.
- La resistencia bacteriana ha reducido la eficacia de los antibióticos macrolidos existentes.
Objetivo del estudio:
- Desarrollar una vía práctica y totalmente sintética para los antibióticos macrólidos.
- Permitir la síntesis de diversas estructuras de macrólidos no accesibles mediante métodos tradicionales.
Principales métodos:
- Un conjunto convergente de bloques de construcción químicos simples.
- Síntesis de más de 300 nuevos candidatos a antibióticos macrolides y el candidato clínico solitromicina.
Principales resultados:
- El enfoque convergente desarrollado permite la síntesis de diversas estructuras de macrólidos.
- La mayoría de los compuestos sintetizados mostraron actividad antibiótica.
- Algunos compuestos fueron efectivos contra las cepas bacterianas resistentes a los macrolides actuales.
Conclusiones:
- La química descrita proporciona una plataforma versátil para el descubrimiento de nuevos antibióticos macrólidos.
- Esta estrategia sintética también puede ser aplicable para la fabricación de nuevos antibióticos.
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