Synthesis, antimycobacterial and antibacterial evaluation of l-[(1R, 2S)-2-fluorocyclopropyl]fluoroquinolone derivatives containing an oxime functional moiety

• 9a1 and 9b3 have good in vitro activity against three MTB and MDR-MTB strains.
• 9a1 exhibits potent activity against Gram-positive strains including MRSA and MRSE.
• 9a1 shows considerable in vivo efficacy against six clinical isolate strains.

A series of novel 1-[(1R, 2S)-2-fluorocyclopropyl]fluoroquinolone derivatives 9a–d containing an oxime functional moiety were synthesized and evaluated for their biological activity. Our results reveal that 9a1 and 9b3 have good in vitro activity against MTB H37Rv ATCC 27294 (MIC: 0.25 μg/mL) and two MDR-MTB clinical isolates (MICs: 0.065–0.125 μg/mL). Most of 9a–d show potent activity against Escherichia coli and Klebsiella pneumoniae (MICs: <0.008–4 μg/mL) except extended-spectrum β-lactamase-producing strains. Especially, 9a1 and 9d4 possessing excellent in vitro activity against all of the fourteen Gram-positive strains including MRSA and MRSE (MICs: <0.008–2 μg/mL) comparable to or better than the four reference drugs, show considerable in vivo efficacy against five Gram-negative and Gram-positive isolate strains (ED50s: 11.43–26.04 mg/kg).

27 1-[(1R, 2S)-2-fluorocyclopropyl]fluoroquinolones were synthesized. 9a1 shows excellent in vitro activity against MTB/MDR-MTB and Gram-positive strains including MRSA and MRSE, and considerable in vivo efficacy against six isolate strains.Figure optionsDownload as PowerPoint slide