Liu Hongmin, Huang Ju, Wang Jiayang, Wang Minghua, Liu Mingliang, Wang Bin, Guo Huiyuan, Lu Yu
New Drug Research & Development Center, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China.
New Drug Research & Development Center, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China; Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Eur J Med Chem. 2014 Oct 30;86:628-38. doi: 10.1016/j.ejmech.2014.09.029. Epub 2014 Sep 9.
A series of novel 1-[(1R, 2S)-2-fluorocyclopropyl]fluoroquinolone derivatives 9a-d containing an oxime functional moiety were synthesized and evaluated for their biological activity. Our results reveal that 9a1 and 9b3 have good in vitro activity against MTB H37Rv ATCC 27294 (MIC: 0.25 μg/mL) and two MDR-MTB clinical isolates (MICs: 0.065-0.125 μg/mL). Most of 9a-d show potent activity against Escherichia coli and Klebsiella pneumoniae (MICs: <0.008-4 μg/mL) except extended-spectrum β-lactamase-producing strains. Especially, 9a1 and 9d4 possessing excellent in vitro activity against all of the fourteen Gram-positive strains including MRSA and MRSE (MICs: <0.008-2 μg/mL) comparable to or better than the four reference drugs, show considerable in vivo efficacy against five Gram-negative and Gram-positive isolate strains (ED50s: 11.43-26.04 mg/kg).
合成了一系列含有肟官能团的新型1-[(1R, 2S)-2-氟环丙基]氟喹诺酮衍生物9a-d，并对其生物活性进行了评估。我们的结果表明，9a1和9b3对结核分枝杆菌H37Rv ATCC 27294具有良好的体外活性（MIC：0.25μg/mL），对两株耐多药结核分枝杆菌临床分离株也有良好活性（MIC：0.065 - 0.125μg/mL）。除产超广谱β-内酰胺酶菌株外，9a-d中的大多数对大肠杆菌和肺炎克雷伯菌显示出强效活性（MIC：<0.008 - 4μg/mL）。特别是，9a1和9d4对包括耐甲氧西林金黄色葡萄球菌和耐甲氧西林表皮葡萄球菌在内的所有14株革兰氏阳性菌株均具有优异的体外活性（MIC：<0.008 - 2μg/mL），与四种参考药物相当或更好，对五株革兰氏阴性和革兰氏阳性分离菌株显示出相当的体内疗效（ED50：11.43 - 26.04mg/kg）。
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