Design, synthesis and anti-TB and anti-bacterial activity of Ciprofloxacin derivatives containing N -(amino)piperazine moieties

Quinolones and rifamycins represent two classes of the most potent antibiotic against bacterial infections. In this study, the N -(amino)piperazine moieties from rifamycins were incorporated into the ciprofloxacin core according to the hybrid strategy, and different substituents were introduced to the N -(amino)piperazine to explore their influence to the anti-TB and antibacterial potency. Compounds 1k with cyclohexyl group (MIC = 0.28 μM) and 3e with N -methyl- N -isopropyl (MIC = 0.60 μM) group showed comparable anti-TB activity to CPFX (MIC = 0.34 μM). Compound 1d (MIC = 2～8 μg/mL) was 4～> 32 fold more potent than CPFX (MIC = 16～> 64 μg/mL) against MRSA and VRE E.fm . Currently, compounds 1d and 1k were employed as new antibacterial and anti-TB leads for further optimization, respectively. Graphical Abstract