Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Daru. 2012 Aug 30;20(1):16. doi: 10.1186/2008-2231-20-16.
Piperazinyl quinolones such as ciprofloxacin, ofloxacin and levofloxacin are an important group of quinolone antimicrobials which are widely used in the treatment of various infectious diseases. In the present study, we synthesized a new series of levofloxacin derivatives and evaluated their antibacterial activities.
The N-substituted analogs of levofloxacin 6a-j were prepared by nucleophilic reaction of N-desmethyl levofloxacin 11 with thienylethyl bromide derivatives 8 or 9. All target compounds were tested using conventional agar dilution method in comparison to levofloxacin and N-desmethyl levofloxacin and their MIC values were determined against a panel of Gram-positive and Gram-negative bacteria.
All compounds showed significant antibacterial activities against Gram-positive bacteria (MIC = 0.04-6.25 μg/mL); however, the activity against Gram-negative bacteria was lower (MIC = 1.56-100 μg/mL). As is evident from the data, oxime derivatives 6e, 6h and 6i are superior in inhibiting the growth of Gram-positive bacteria (MIC = 0.04-0.19 μg/mL), and their activities were found to be 5-25 times better than N-desmethyl levofloxacin 11 and equal or better than levofloxacin 4.
We have designed and synthesized novel quinolone derivatives bearing functionalized thienylethyl moiety on the piperazine ring of levofloxacin. The results of antibacterial screening against Gram-positive and Gram-negative bacteria revealed that the introduction of functionalized thienylethyl moiety on the piperazine ring of levofloxacin can improve the activity against Gram-positive bacteria. Gram-positive bacteria are responsible for a wide range of infectious diseases, and rising resistance in this group is causing increasing concern. Thus, this study introduces structural features of levofloxacin scaffold for development of new candidates in the field of anti-Gram positive chemotherapy.
哌嗪基喹诺酮类药物如环丙沙星、氧氟沙星和左氧氟沙星是一类重要的喹诺酮类抗菌药物，广泛用于治疗各种感染性疾病。在本研究中，我们合成了一系列新的左氧氟沙星衍生物，并评估了它们的抗菌活性。
通过亲核反应，将 N-去甲基左氧氟沙星 11 与噻吩乙基溴衍生物 8 或 9 反应，制备得到左氧氟沙星的 N-取代类似物 6a-j。采用常规琼脂稀释法，将所有目标化合物与左氧氟沙星和 N-去甲基左氧氟沙星进行比较，测定其对一组革兰氏阳性和革兰氏阴性细菌的 MIC 值。
所有化合物对革兰氏阳性菌均显示出显著的抗菌活性（MIC=0.04-6.25μg/mL）；然而，对革兰氏阴性菌的活性较低（MIC=1.56-100μg/mL）。从数据可以明显看出，肟衍生物 6e、6h 和 6i 对革兰氏阳性菌的生长抑制作用更强（MIC=0.04-0.19μg/mL），其活性比 N-去甲基左氧氟沙星 11 高 5-25 倍，与左氧氟沙星 4 相当或更好。
我们设计并合成了新型喹诺酮衍生物，在左氧氟沙星的哌嗪环上引入了功能化的噻吩乙基取代基。对革兰氏阳性和革兰氏阴性菌的抗菌筛选结果表明，在左氧氟沙星的哌嗪环上引入功能化的噻吩乙基取代基可以提高对革兰氏阳性菌的活性。革兰氏阳性菌是多种感染性疾病的病原体，其耐药性的增加引起了越来越多的关注。因此，本研究为开发新型革兰氏阳性化疗候选药物引入了左氧氟沙星支架的结构特征。
