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Synthesis and antimicrobial evaluation of new nitric oxide‐donating fluoroquinolone/oxime hybrids
Author(s) -
Aziz Hossameldin A.,
Moustafa Gamal A. I.,
AbuoRahma Gamal ElDin A.,
Rabea Safwat M.,
Hauk Glenn,
Krishna Vagolu S.,
Sriram Dharmarajan,
Berger James M.,
Abbas Samar H.
Publication year - 2021
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.202000180
Subject(s) - dna gyrase , chemistry , oxime , minimum inhibitory concentration , ciprofloxacin , ketone , nitric oxide , antibacterial activity , staphylococcus aureus , antimicrobial , nuclear chemistry , stereochemistry , antibiotics , bacteria , organic chemistry , biochemistry , escherichia coli , biology , genetics , gene
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.