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Medicinal Chemistry Research

, Volume 28, Issue 8, pp 1272–1283 | Cite as

New fluoroquinolones/nitric oxide donor hybrids: design, synthesis and antitubercular activity

  • Hossameldin A. Aziz
  • Gamal A. I. Moustafa
  • Samar H. AbbasEmail author
  • Glenn Hauk
  • Vagolu Siva Krishna
  • Dharmarajan Sriram
  • James M. Berger
  • Gamal El-Din A. Abuo-RahmaEmail author
Original Research
  • 67 Downloads

Abstract

New nitric oxide (NO) donating fluoroquinolones/nitrate ester hybrids were prepared and their structures were characterized by various spectroscopic and analytical tools. The release of NO from the prepared nitrate esters was measured using the modified Griess colorimetric method. Evaluation of antitubercular activity showed that most of tested compounds exhibited comparable or higher activity than the parent fluoroquinolones. Compounds 2b, 3a, 4a, 5a, and 2d showed better activity than ciprofloxacin. Nevertheless, none of the new compounds were superior to the parent fluoroquinolones in terms of DNA cleavage stimulation in mycobacteria. The additional growth inhibition effect that is distinct from gyrase poisoning may be due to release of NO or enhancement of lipophilicity. These data are augmented by docking results where the docked compounds did not exert additional significant bindings over the parent fluoroquinolones.

Keywords

Fluoroquinolones Antitubercular Nitric oxide (NO) Cleavable DNA complex Molecular docking 

Notes

Acknowledgements

We thank Dr. Safwat Rabea (Faculty of Pharmaceutical Sciences, The University of British Columbia, Canada), for measuring the high-resolution mass spectra for the synthesized compounds. The biochemical analysis of gyrase and the synthesized inhibitors was supported by the NCI (R01-CA077373, to J.M.B.).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Medicinal ChemistryFaculty of Pharmacy, Minia UniversityMiniaEgypt
  2. 2.Department of Biophysics and Biophysical ChemistryJohns Hopkins University, School of MedicineBaltimoreUSA
  3. 3.Department of PharmacyBirla Institute of Technology and Science, Pilani, Hyderabad CampusHyderabadIndia

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