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Synthesis, antimicrobial activity, and molecular docking study of fluorine-substituted indole-based imidazolines

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Abstract

A series of 2- or 3-(4,5-dihydro-1H-imidazol-2-yl)-1H-indole derivatives were synthesized, characterized, and evaluated for their in vitro antibacterial and antifungal activities. Additionally, the synthesized compounds were docked into the II DNA gyrase B active site, and their predicted binding modes were inspected. Inhibitory activity were tested against two species of Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa), two species of Gram-positive bacteria (Staphylococcus aureus, Listeria monocytogenes) and two fungi (Candida albicans, Aspergillus niger) using the broth microdilution method. The fluorine-substituted 2-(2-imidazolyl)indole 2b was found to be the most potent antibacterial compound against E. coli and S. aureus strains (MIC value 80 μg/mL). Compounds showed better activity against Gram-positive bacteria compared to Gram-negative bacteria. The docking results predicted that the imidazoline-indole hybrid moiety bind to the active site protein ATP-binding pocket from E. coli and S. aureus with good interaction energy scores. The significant loss of antibacterial activity for some imidazoline-indole analogs could be attributed to several nonoptimal enzyme interactions, including poor hydrogen bonds provided by Asp73 (E. coli gyrase numbering) or Asp81 (S. aureus gyrase numbering) and an associated water molecule.

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Acknowledgements

The present work is partially supported by CONACYT grant 179187 and Programa de Fortalecimiento Académico del Posgrado de Alta Calidad.

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Authors and Affiliations

  1. Departamento de Química, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Apartado 14-740, Mexico City, 07000, Mexico

    Humberto L. Mendoza-Figueroa, Maria Trinidad Serrano-Alva, Gelacio Martínez-Gudiño, Nadia A. Pérez-Rojas & Martha S. Morales-Ríos

  2. Programa de Posgrado en Farmacología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Apartado 14-740, Mexico City, 07000, Mexico

    Humberto L. Mendoza-Figueroa, Maria Trinidad Serrano-Alva, Gelacio Martínez-Gudiño & Martha S. Morales-Ríos

  3. Departamento de Microbiología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Apartado 42-186, Mexico City, 11340, Mexico

    Gerardo Aparicio-Ozores

  4. Área Académica de Química, Universidad Autónoma del Estado de Hidalgo, Mineral de la Reforma, Hidalgo, 42184, Mexico

    Oscar R. Suárez-Castillo

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  1. Humberto L. Mendoza-Figueroa
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  2. Maria Trinidad Serrano-Alva
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  3. Gerardo Aparicio-Ozores
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Correspondence to Martha S. Morales-Ríos.

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Mendoza-Figueroa, H.L., Serrano-Alva, M.T., Aparicio-Ozores, G. et al. Synthesis, antimicrobial activity, and molecular docking study of fluorine-substituted indole-based imidazolines. Med Chem Res 27, 1624–1633 (2018). https://doi.org/10.1007/s00044-018-2177-x

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  • DOI: https://doi.org/10.1007/s00044-018-2177-x

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