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Medicinal Chemistry Research

, Volume 27, Issue 6, pp 1624–1633 | Cite as

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

  • Humberto L. Mendoza-Figueroa
  • Maria Trinidad Serrano-Alva
  • Gerardo Aparicio-Ozores
  • Gelacio Martínez-Gudiño
  • Oscar R. Suárez-Castillo
  • Nadia A. Pérez-Rojas
  • Martha S. Morales-Ríos
Original Research
  • 293 Downloads

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.

Keywords

Imidazole Indole Tautomers Antibacterial activity Docking studies Gyrase B 

Notes

Acknowledgements

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

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

44_2018_2177_MOESM1_ESM.pdf (2.2 mb)
Supplementary Information

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Humberto L. Mendoza-Figueroa
    • 1
    • 2
  • Maria Trinidad Serrano-Alva
    • 1
    • 2
  • Gerardo Aparicio-Ozores
    • 3
  • Gelacio Martínez-Gudiño
    • 1
    • 2
  • Oscar R. Suárez-Castillo
    • 4
  • Nadia A. Pérez-Rojas
    • 1
  • Martha S. Morales-Ríos
    • 1
    • 2
  1. 1.Departamento de QuímicaCentro de Investigación y de Estudios Avanzados del Instituto Politécnico NacionalMexico CityMexico
  2. 2.Programa de Posgrado en FarmacologíaCentro de Investigación y de Estudios Avanzados del Instituto Politécnico NacionalMexico CityMexico
  3. 3.Departamento de Microbiología, Escuela Nacional de Ciencias BiológicasInstituto Politécnico NacionalMexico CityMexico
  4. 4.Área Académica de QuímicaUniversidad Autónoma del Estado de HidalgoHidalgoMexico

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