• antibiotics;
  • chirality;
  • drug design;
  • medicinal chemistry;
  • quinolones


A series of novel (R)/(S)-7-(3-alkoxyimino-2-aminomethyl-1-azetidinyl)fluoroquinolone derivatives were synthesized and evaluated for their in vitro antibacterial activity against representative strains. Our results reveal that 12 of the target compounds generally show better activity (MIC: <0.008–0.5 μg mL−1) against the tested Gram-positive strains including MRSA and MRSE than levofloxacin (LVFX, MIC: 0.125–8 μg mL−1). Their activity is similar to that of gemifloxacin (GMFX, MIC: <0.008–4 μg mL−1). However, they are generally less active than the two reference drugs against Gram-negative strains. Moreover, against clinical strains of S. aureus including MRSA and S. epidermidis including MRSE, the MIC50 values (0.06–16 μg mL−1) and MIC90 values (0.5–32 μg mL−1) of compounds 16 w, y, and z are 2–8- and 2–16-fold less than LVFX, respectively, and 16 w (MIC90 range: 0.5–4 μg mL−1) was also found to be more active than GMFX (MIC90 range: 1–8 μg mL−1).