Docking studies on novel analogs of quinolones

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J Pharm Pharmacogn Res 6(5): 386-391, 2018. DOI: https://doi.org/10.56499/jppres18.368_6.5.386 Original Article Docking studies on novel analogs of quinolones against DNA gyrase of Escherichia coli [Estudios de acoplamiento molecular de nuevos análogos de quinolonas a la ADN girasa de Escherichia coli] Cristian Davila1, Lorena Llach2, Guillermo Salgado-Moran3, Rodrigo Ramirez-Tagle4* 1Escuela de Química y Farmacia, Universidad Andrés Bello, Republica … Continue reading Docking studies on novel analogs of quinolones

J Pharm Pharmacogn Res 6(5): 386-391, 2018.

DOI: https://doi.org/10.56499/jppres18.368_6.5.386

Original Article

Docking studies on novel analogs of quinolones against DNA gyrase of Escherichia coli

[Estudios de acoplamiento molecular de nuevos análogos de quinolonas a la ADN girasa de Escherichia coli]

Cristian Davila1, Lorena Llach2, Guillermo Salgado-Moran3, Rodrigo Ramirez-Tagle4*

1Escuela de Química y Farmacia, Universidad Andrés Bello, Republica 237, Santiago, Chile.
2Facultad de Salud, Universidad Bernardo O´Higgins, General Gana 1780, Santiago, Chile. 
 3Facultad de Ciencias Exactas, Departamento de Química, Universidad Andrés Bello, Autopista Concepción – Talcahuano 7100, Concepción, Chile.
4Facultad de Ingeniería, Ciencia y Tecnología, Universidad Bernardo O´Higgins, General, Av. Viel 1497, Santiago, Chile.

*E-mail: rramirez@ubo.cl

Abstract

Context: Bacterial resistance to antibiotics is the inevitable consequence of the use of antimicrobial agents. Thus, quinolones are an important class of antibacterials; these agents generally consist of a 1-subtituted-1,4-dihydro-4-oxopyridine-3-carboxylic acid moiety combined with an aromatic or heteroaromatic ring fused at the 5- and 6-position.

Aims: To determine the binding of quinolones to DNA gyrase of Escherichia coli.

Methods: An analysis was performed using an in silico approach to determine, by docking calculations and energy descriptors, the conformer of 4‐oxo‐1,4‐dihydroquinoline skeleton that forms the most stable complex with DNA gyrase of E. coli.

Results: The complex shows that the pose of the quinolones coincides with the amino acid residues Asp87, Thr88, Arg91 and Met92, which is expected to be critical in the binding of quinolones to DNA gyrase of E. coli. A series of quinolones were computationally designed, and the interactions between the quinolones and the amino acid residues of the DNA gyrase were calculated.

Conclusions: Among the designed compounds, compounds 105 and 115 exhibit higher binding energy values and interact with amino acids Asp87, Thr88, Arg91 and Met92.

Keywords: Arguslab; DNA gyrase; docking; Escherichia coli; quinolones.

[Supplementary Data]

Resumen

Contexto: La resistencia bacteriana a los antibióticos es la consecuencia inevitable del uso de agentes antimicrobianos. Por lo tanto, las quinolonas son una clase importante de antibacterianos; estos agentes generalmente consisten en un resto ácido 1-sustituido-1,4-dihidro-4-oxopiridina-3-carboxílico combinado con un anillo aromático o heteroaromático fusionado en las posiciones 5 y 6.

Objetivos: Determinar la unión de quinolonas a ADN girasa de Escherichia coli.

Métodos: Se realizó un análisis utilizando un enfoque in silico para determinar, mediante cálculos de unión y descriptores de energía, el confórmero del esqueleto de 4-oxo-1,4-dihidroquinolina que forma el complejo más estable con la ADN girasa de E. coli.

Resultados: El complejo muestra que la postura de las quinolonas coincide con los residuos de aminoácidos Asp87, Thr88, Arg91 y Met92, que se espera que sean críticos en la unión de quinolonas a ADN girasa de E. coli. Se diseñó computacionalmente una serie de quinolonas, y se calcularon las interacciones entre las quinolonas y los residuos de aminoácidos de la ADN girasa.

Conclusiones: Entre los compuestos diseñados, los compuestos 105 y 115 exhiben valores de energía de unión más elevados e interactúan con los aminoácidos Asp87, Thr88, Arg91 y Met92.

Palabras Clave: acoplamiento molecular; ADN girasa; Arguslab; Escherichia coli; quinolonas.

[Supplementary Data]

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Supplementary Data:

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Citation Format: Davila C, Llach L, Salgado-Moran G, Ramirez-Tagle R (2018) Docking studies on novel analogs of quinolones against DNA gyrase of Escherichia coli. J Pharm Pharmacogn Res 5(6): 386–391. DOI: https://doi.org/10.56499/jppres18.368_6.5.386

© 2018 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

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