新型2-羟基-3-(硝基咪唑基)丙基衍生喹诺酮的设计、合成、抗菌评价及对接研究
Design, synthesis, antibacterial evaluation and docking study of novel 2-hydroxy-3-(nitroimidazolyl)-propyl-derived quinolone.
作者信息
Li Qing, Xing Junhao, Cheng Haibo, Wang Hui, Wang Jing, Wang Shuai, Zhou Jinpei, Zhang Huibin
机构信息
Center of Drug Discovery, China Pharmaceutical University, Nanjing, 210009, China.
出版信息
Chem Biol Drug Des. 2015 Jan;85(1):79-90. doi: 10.1111/cbdd.12395. Epub 2014 Aug 16.
A novel series of 2-hydroxy-3-(nitroimidazolyl)-propyl-derived quinolones 6a-o were synthesized and evaluated for their in vitro antibacterial activity. Most of the target compounds exhibited potent activity against Gram-positive strains. Among them, moxifloxacin analog 6n displayed the most potent activity against Gram-positive strains including S. epidermidis (MIC = 0.06 μg/mL), MSSE (MIC = 0.125 μg/mL), MRSE (MIC = 0.03 μg/mL), S. aureus (MIC = 0.125 μg/mL), MSSA (MIC = 0.125 μg/mL), (MIC = 2 μg/mL). Its activity against MRSA was eightfold more potent than reference drug gatifloxacin. Finally, docking study of the target compound 6n revealed that the binding model of quinolone nucleus was similar to that of gatifloxacin and the 2-hydroxy-3-(nitroimidazolyl)-propyl group formed two additional hydrogen bonds.
合成了一系列新型的2-羟基-3-(硝基咪唑基)丙基衍生喹诺酮类化合物6a-o，并对其体外抗菌活性进行了评估。大多数目标化合物对革兰氏阳性菌表现出强效活性。其中，莫西沙星类似物6n对包括表皮葡萄球菌（MIC = 0.06 μg/mL）、耐甲氧西林表皮葡萄球菌（MIC = 0.125 μg/mL）、耐甲氧西林金黄色葡萄球菌（MIC = 0.03 μg/mL）、金黄色葡萄球菌（MIC = 0.125 μg/mL）、甲氧西林敏感金黄色葡萄球菌（MIC = 0.125 μg/mL）、（MIC = 2 μg/mL）在内的革兰氏阳性菌表现出最强大的活性。其对耐甲氧西林金黄色葡萄球菌的活性比参考药物加替沙星强八倍。最后，目标化合物6n的对接研究表明，喹诺酮核的结合模式与加替沙星相似，且2-羟基-3-(硝基咪唑基)丙基形成了另外两个氢键。
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