Design, synthesis, and in vitro antibacterial activity of fluoroquinolone derivatives containing a chiral 3-(alkoxyimino)-2-(aminomethyl)azetidine moiety.
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 MIC(50) values (0.06-16 μg mL(-1)) and MIC(90) 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 (MIC(90) range: 0.5-4 μg mL(-1)) was also found to be more active than GMFX (MIC(90) range: 1-8 μg mL(-1)).
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, 100050 Beijing, China.
Kai
K
Lv
Yexin
Y
Sun
Lanyin
L
Sun
Zengquan
Z
Wei
Huiyuan
H
Guo
Jinwei
J
Wu
Mingliang
M
Liu
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001384:Azetidines / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D024841:Fluoroquinolones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D001384:Azetidines; D024841:Fluoroquinolones