Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China.
Bioorg Med Chem Lett. 2011 Feb 1;21(3):928-31. doi: 10.1016/j.bmcl.2010.12.073. Epub 2010 Dec 19.
We report herein the design and synthesis of novel 7-(3-alkoxyimino-5-amino/methylaminopiperidin-1-yl)fluoroquinolone derivatives based on the structures of new fluoroquinolones IMB and DZH. The antibacterial activity of these newly synthesized compounds was also evaluated and compared with gemifloxacin, ciprofloxacin, and levofloxacin. Results revealed that all of the target compounds 10-27 have good potency in inhibiting the growth of Staphylococcus aureus including MSSA (MIC: 0.125-8 μg/mL), Staphylococcus epidermidis including MRSE (MIC: 0.25-16 μg/mL), Streptococcus pneumoniae (MIC: 0.125-4 μg/mL), and Escherichia coli (MIC: 0.25-0.5 μg/mL). In particular, some compounds showed useful activity against several fluoroquinolone-resistant strains, and the most active compound 15 was found to be 16-128, 2-32, and 4-8-fold more potent than the three reference drugs against fluoroquinolone-resistant MSSA, MRSA, and MRSE.
我们在此报告了基于新型氟喹诺酮 IMB 和 DZH 结构的新型 7-(3-烷氧基亚氨基-5-氨基/甲氨基哌啶-1-基)氟喹诺酮衍生物的设计和合成。还评估了这些新合成化合物的抗菌活性，并与加替沙星、环丙沙星和左氧氟沙星进行了比较。结果表明，所有目标化合物 10-27 对金黄色葡萄球菌（包括 MSSA，MIC：0.125-8 μg/mL）、表皮葡萄球菌（包括 MRSE，MIC：0.25-16 μg/mL）、肺炎链球菌（MIC：0.125-4 μg/mL）和大肠杆菌（MIC：0.25-0.5 μg/mL）的生长均具有良好的抑制作用。特别是，一些化合物对几种氟喹诺酮耐药株表现出有用的活性，最活性化合物 15 对氟喹诺酮耐药 MSSA、MRSA 和 MRSE 的活性分别比三种参比药物强 16-128、2-32 和 4-8 倍。
