1. Synthesis and antimicrobial evaluation of new nitric oxide-donating fluoroquinolone/oxime hybrids.
- Author
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Aziz HA, Moustafa GAI, Abuo-Rahma GEA, Rabea SM, Hauk G, Krishna VS, Sriram D, Berger JM, and Abbas SH
- Subjects
- Anti-Bacterial Agents chemical synthesis, Anti-Bacterial Agents chemistry, Antitubercular Agents chemical synthesis, Antitubercular Agents chemistry, Antitubercular Agents pharmacology, Bacteria drug effects, Ciprofloxacin pharmacology, Fluoroquinolones chemical synthesis, Fluoroquinolones chemistry, Microbial Sensitivity Tests, Models, Molecular, Nitric Oxide metabolism, Nitric Oxide Donors chemical synthesis, Nitric Oxide Donors chemistry, Oximes chemical synthesis, Oximes chemistry, Structure-Activity Relationship, Anti-Bacterial Agents pharmacology, Fluoroquinolones pharmacology, Nitric Oxide Donors pharmacology, Oximes pharmacology
- 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., (© 2020 Deutsche Pharmazeutische Gesellschaft.)
- Published
- 2021
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