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

Autor: Aziz HA; Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, Minia, Egypt., Moustafa GAI; Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, Minia, Egypt., Abuo-Rahma GEA; Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, Minia, Egypt.; Department of Pharmaceutical Chemistry, Deraya University, New Minia, Minia, Egypt., Rabea SM; Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, Minia, Egypt., Hauk G; Department of Biophysics and Biophysical Chemistry, School of Medicine, John Hopkins University, Baltimore, Maryland., Krishna VS; Department of Pharmacy, Birla Institute of Technology and Science, Pilani, Hyderabad Campus, Hyderabad, India., Sriram D; Department of Pharmacy, Birla Institute of Technology and Science, Pilani, Hyderabad Campus, Hyderabad, India., Berger JM; Department of Biophysics and Biophysical Chemistry, School of Medicine, John Hopkins University, Baltimore, Maryland., Abbas SH; Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, Minia, Egypt.
Jazyk: angličtina
Zdroj: Archiv der Pharmazie [Arch Pharm (Weinheim)] 2021 Jan; Vol. 354 (1), pp. e2000180. Date of Electronic Publication: 2020 Sep 21.
DOI: 10.1002/ardp.202000180
Abstrakt: 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.)
Databáze: MEDLINE
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