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 derivatives2band2eand oximes3band3dexhibited somewhat higher activity than their respective parent fluoroquinolones. Mycobacterial DNA cleavage studies and molecular modeling ofMycobacterium tuberculosisDNA gyrase were pursued to explain the observed bioactivity. More important, antibacterial evaluation showed that oximes3c-eare highly potent againstKlebsiella pneumoniae, with minimum inhibitory concentration (MIC) values of 0.06, 0.08, and 0.034 mu M, respectively, whereas ketone2cand oxime4care more active againstStaphylococcus aureusthan ciprofloxacin (MIC values: 0.7, 0.38, and 1.6 mu M, respectively). Notably, the antipseudomonal activities of compounds2aand4cwere much higher than those of their respective parent fluoroquinolones.

Automated summary

A new series of nitric oxide-donating fluoroquinolone/oximes were synthesized, showing higher activity in antitubercular and antibacterial evaluations. Mycobacterial DNA cleavage and molecular modeling were used to explain the bioactivity observed. Oximes3c-e were highly potent against Klebsiella pneumoniae, while ketone2c and oxime4c were more active against Staphylococcus aureus than ciprofloxacin.