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Ejercicio basado en la afinidad para los inhibidores de la transglucosilasa bacteriana

Wei-Shen Wu^1,2, Wei-Chieh Cheng², Ting-Jen R Cheng²

¹Graduate Institute of Life Sciences, National Defense Medical Center , 161 Minquan E. Road, Section 6, Neihu, Taipei 114, Taiwan.

Journal of the American Chemical Society

|February 8, 2018

Resumen

Los investigadores desarrollaron un nuevo método para encontrar nuevos antibióticos dirigidos a la transglucosilasa bacteriana. Esta prueba identificó compuestos antibacterianos potentes, incluidos los derivados de la benastatina y la albofungina, eficaces contra las bacterias resistentes.

Área de la Ciencia:

Química medicinal
Microbiología
Descubrimiento de drogas

Sus antecedentes:

La resistencia a los antibióticos es una crisis global que requiere el desarrollo de nuevos agentes antimicrobianos.
Hay una necesidad médica crítica no satisfecha de nuevos antibióticos para combatir las infecciones bacterianas resistentes.

Objetivo del estudio:

Desarrollar un método de detección de ligandos basado en la afinidad para identificar nuevos antibióticos.
Para dirigirse a la enzima transglicosilasa de superficie bacteriana no explorada anteriormente.
Para aislar potentes compuestos antibacterianos de las complejas bibliotecas de productos naturales.

Principales métodos:

Utilizó proteínas de unión a la penicilina inmovilizadas en cuentas para el cribado basado en la afinidad.
Se utiliza la espectrometría de masas para la identificación y caracterización de compuestos.
Se han realizado ensayos comparativos utilizando como inhibidores de referencia la moenomicina A y los análogos de la salicilanilida.

Principales resultados:

Se han aislado con éxito cuatro compuestos antibacterianos potentes: derivados de la benastatina (11-13) y la albofungina (14).
Los compuestos 11 y 14 demostraron una eficacia de amplio espectro contra las bacterias Gram-positivas y Gram-negativas.
Estos compuestos fueron efectivos contra patógenos desafiantes, incluidos Acinetobacter baumannii, Clostridium difficile y Staphylococcus aureus, incluidas las cepas resistentes a los medicamentos, con concentraciones mínimas inhibidoras submicromolares a nanomolares.

Conclusiones:

El método de detección basado en la afinidad desarrollado es eficaz para descubrir nuevos antibióticos.
Los derivados de la benastatina y la albofungina representan candidatos prometedores para el desarrollo de nuevos antibióticos.
Estos compuestos muestran un potencial significativo para el tratamiento de infecciones causadas por bacterias multirresistentes.

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