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

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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.

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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.).

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Authors and Affiliations

  1. Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, Minia, Minia-61519, Egypt

    Hossameldin A. Aziz, Gamal A. I. Moustafa, Samar H. Abbas & Gamal El-Din A. Abuo-Rahma

  2. Department of Biophysics and Biophysical Chemistry, Johns Hopkins University, School of Medicine, Baltimore, MD, 21205, USA

    Glenn Hauk & James M. Berger

  3. Department of Pharmacy, Birla Institute of Technology and Science, Pilani, Hyderabad Campus, Hyderabad, India

    Vagolu Siva Krishna & Dharmarajan Sriram

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  1. Hossameldin A. Aziz
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  2. Gamal A. I. Moustafa
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  3. Samar H. Abbas
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  4. Glenn Hauk
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Correspondence to Samar H. Abbas or Gamal El-Din A. Abuo-Rahma.

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Aziz, H.A., Moustafa, G.A.I., Abbas, S.H. et al. New fluoroquinolones/nitric oxide donor hybrids: design, synthesis and antitubercular activity. Med Chem Res 28, 1272–1283 (2019). https://doi.org/10.1007/s00044-019-02372-y

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