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Synthesis and antimicrobial evaluation of new nitric oxide‐donating fluoroquinolone/oxime hybrids

Synthesis and antimicrobial evaluation of new nitric oxide‐donating fluoroquinolone/oxime hybrids
Synthesis and antimicrobial evaluation of new nitric oxide‐donating fluoroquinolone/oxime hybrids
A new series of nitric oxide‐donating fluoroquinolone/oximes was prepared in this study. The nitric oxide release from the prepared compounds was measured using a modified Griess colorimetric method. The antitubercular evaluation of the synthesized compounds indicated that ketone derivatives 2b and 2e and oximes 3b and 3d exhibited somewhat higher activity than their respective parent fluoroquinolones. Mycobacterial DNA cleavage studies and molecular modeling of Mycobacterium tuberculosis DNA gyrase were pursued to explain the observed bioactivity. More important, antibacterial evaluation showed that oximes 3c–e are highly potent against Klebsiella pneumoniae, with minimum inhibitory concentration (MIC) values of 0.06, 0.08, and 0.034 µM, respectively, whereas ketone 2c and oxime 4c are more active against Staphylococcus aureus than ciprofloxacin (MIC values: 0.7, 0.38, and 1.6 µM, respectively). Notably, the antipseudomonal activities of compounds 2a and 4c were much higher than those of their respective parent fluoroquinolones.
antibacterial, antitubercular, cleavable DNA complex, fluoroquinolones, nitric oxide
1521-4184
1-14
Aziz, Hossameldin
c5507861-a494-42b2-941b-9d3776ddfda0
Moustafa, Gamal
1a452cdc-4856-4243-9864-b391fb115f07
Abuo-Rahma, Gamal
b964d0a7-df3c-4f6f-9f60-0bda1234c0e2
M. Rabea, Safwat
4ece811d-2c7f-4140-8e1c-4afeb8640c05
Hauk, Glenn
ed8a0f28-ee9b-4cf0-b2a0-241d3b467331
Krishna, Vagulo S.
37c07927-cb30-417c-92cd-f13deb008eb9
Sriram, Dharmarajan
ef0f17ba-4104-44ee-a165-d628ca33323d
Berger, James M.
12dcfffa-b794-4fd6-894a-5ba42a5728ed
Abbas, Samar
f1a0c890-9b50-4d32-ad07-9c0b49e2784b
Aziz, Hossameldin
c5507861-a494-42b2-941b-9d3776ddfda0
Moustafa, Gamal
1a452cdc-4856-4243-9864-b391fb115f07
Abuo-Rahma, Gamal
b964d0a7-df3c-4f6f-9f60-0bda1234c0e2
M. Rabea, Safwat
4ece811d-2c7f-4140-8e1c-4afeb8640c05
Hauk, Glenn
ed8a0f28-ee9b-4cf0-b2a0-241d3b467331
Krishna, Vagulo S.
37c07927-cb30-417c-92cd-f13deb008eb9
Sriram, Dharmarajan
ef0f17ba-4104-44ee-a165-d628ca33323d
Berger, James M.
12dcfffa-b794-4fd6-894a-5ba42a5728ed
Abbas, Samar
f1a0c890-9b50-4d32-ad07-9c0b49e2784b

Aziz, Hossameldin, Moustafa, Gamal, Abuo-Rahma, Gamal, M. Rabea, Safwat, Hauk, Glenn, Krishna, Vagulo S., Sriram, Dharmarajan, Berger, James M. and Abbas, Samar (2021) Synthesis and antimicrobial evaluation of new nitric oxide‐donating fluoroquinolone/oxime hybrids. Archiv der Pharmazie, 354 (1), 1-14, [2000180]. (doi:10.1002/ardp.202000180).

Record type: Article

Abstract

A new series of nitric oxide‐donating fluoroquinolone/oximes was prepared in this study. The nitric oxide release from the prepared compounds was measured using a modified Griess colorimetric method. The antitubercular evaluation of the synthesized compounds indicated that ketone derivatives 2b and 2e and oximes 3b and 3d exhibited somewhat higher activity than their respective parent fluoroquinolones. Mycobacterial DNA cleavage studies and molecular modeling of Mycobacterium tuberculosis DNA gyrase were pursued to explain the observed bioactivity. More important, antibacterial evaluation showed that oximes 3c–e are highly potent against Klebsiella pneumoniae, with minimum inhibitory concentration (MIC) values of 0.06, 0.08, and 0.034 µM, respectively, whereas ketone 2c and oxime 4c are more active against Staphylococcus aureus than ciprofloxacin (MIC values: 0.7, 0.38, and 1.6 µM, respectively). Notably, the antipseudomonal activities of compounds 2a and 4c were much higher than those of their respective parent fluoroquinolones.

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Accepted/In Press date: 31 August 2020
Published date: January 2021
Additional Information: Funding Information: The authors thank Dr. Rehab M Abdel-Baky, Department of Microbiology and Immunology, Minia University, and Mycological Center (AUMC), Faculty of Science, Assiut University, Assiut, Egypt, for their great help in carrying out the antibacterial screening. Publisher Copyright: © 2020 Deutsche Pharmazeutische Gesellschaft
Keywords: antibacterial, antitubercular, cleavable DNA complex, fluoroquinolones, nitric oxide

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Local EPrints ID: 444043
URI: http://eprints.soton.ac.uk/id/eprint/444043
ISSN: 1521-4184
PURE UUID: 4cfda827-a49f-45ff-a4c9-07598fa55589
ORCID for Gamal Moustafa: ORCID iD orcid.org/0000-0002-9940-0033

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Date deposited: 23 Sep 2020 16:31
Last modified: 04 Oct 2022 01:59

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Contributors

Author: Hossameldin Aziz
Author: Gamal Moustafa ORCID iD
Author: Gamal Abuo-Rahma
Author: Safwat M. Rabea
Author: Glenn Hauk
Author: Vagulo S. Krishna
Author: Dharmarajan Sriram
Author: James M. Berger
Author: Samar Abbas

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