In silico screening of flavonoids targeting chromosomal replication initiator protein as a molecular target for new antibiotics in Shigella dysenteriae.

Mohammed Al-Khayyat

doi:10.15649/2346075X.4005

Autores/as

Mohammed Al-Khayyat Biology Department, College of Science, University of Mosul https://orcid.org/0000-0001-7196-637X

DOI:

https://doi.org/10.15649/2346075X.4005

Palabras clave:

AutoDock Vina, Corylin, Modelado por Homología, Molecular Docking

Resumen

Introducción. La proteína DnaA, iniciadora de la replicación cromosómica bacteriana, desempeña un papel fundamental en el ciclo celular, convirtiéndola en un objetivo prometedor para el desarrollo de nuevos antibióticos. Objetivo. Identificar flavonoides con potencial para unirse e inhibir DnaA mediante cribado in silico. Materiales y Métodos. La secuencia de DnaA de Shigella dysenteriae se obtuvo de la base de datos UniProt. Se generó un modelo de homología de DnaA utilizando SWISS-MODEL. La precisión del modelo se evaluó utilizando ERRAT, PROCHECK y Molprobity. El modelo refinado se utilizó en experimentos de acoplamiento molecular con una biblioteca de 300 flavonoides. Las propiedades farmacocinéticas se predijeron utilizando admetSAR 2.0. Resultados. El cribado virtual de 300 flavonoides identificó el flavonoide Corylin como un ligando de alta puntuación con una afinidad de unión superior a la del ADP. El análisis de acoplamiento molecular reveló interacciones clave entre el Corylin y el DnaA, incluyendo puentes de hidrógeno con los residuos T¹⁷⁹, R²³⁶ y R³³⁴, así como interacciones hidrofóbicas con los residuos F¹⁴¹, T¹⁷⁴, G¹⁷⁵, G¹⁷⁷, K¹⁷⁸, H¹⁸⁰ e I³⁰⁵. Discusión. Se predice que el Corylin se absorbe en el tracto gastrointestinal y no parece inhibir el Transportador de Cationes Orgánicos 2 (OCT2). Sin embargo, podría inhibir potencialmente la función de las enzimas del citocromo P450 humano. Conclusiones. El cribado in silico identifica al Corylin como un posible compuesto líder para la inhibición de DnaA, lo que justifica una mayor investigación y validación in vitro e in vivo por su potencial como agente antimicrobiano.

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