目的 为寻找抗菌活性化合物,设计系列7-磷酰基喹诺酮衍生物,探索其合成方法,评价其抗菌活性。方法 在微波辅助下,以磷酸酯与喹诺酮中间体为原料,碱性离子液体[Bmim]OH为催化剂,合成目标化合物;采用2倍稀释法对目标物进行体外抗菌活性筛选。结果 合成了8个结构新颖的喹诺酮衍生物,经IR、1H-NMR、13C-NMR和MS确认结构;活性测试表明,该类衍生物对所测标准菌和耐药菌有潜在抑制活性,其中化合物Ⅱc对金黄色葡萄球菌 (S. aureus) 、大肠埃希菌 (E. coli)、耐氟喹诺酮类大肠杆菌(MREC-1#)及耐氟喹诺酮类大肠杆菌(MREC-2#)的MIC分别为1.6、6.4、12.8和6.4 mg·mL-1,化合物Ⅱg对S. aureus、E. coli、MREC-1#及MREC-2#的MIC分别为1.6、3.2、6.4和6.4 mg·mL-1,尤其对耐药菌的活性优于对照药诺氟沙星(norfloxacin)。结论 该类喹诺酮衍生物对耐药菌的抑制活性显著,值得进一步研究。
Abstract
OBJECTIVE To search more effective antibacterial candidate agents by designing a series of 7-phosphoryl quinolone derivatives,exploring the synthetic methods, and evaluating their antibacterial activities. METHODS The quinolone derivatives were synthesized using phosphate and quinolone intermediates as raw materials and alkaline ionic liquid [Bmim] OH as catalyst with microwave assistance. The antibacterial activities of the products were evaluated by agar dilution method. RESULTS Eight title compounds were prepared, and their structures were clearly established by IR, NMR and MS. The in vitro experiment showed that the derivatives had potential antibacterial activity. Especially, compound Ⅱc showed more potent activities against S. aureus, E. coli, MREC-1# and MREC-2# with minimum inhibitory concentrations (MICs) of 1.6, 6.4, 12.8,6.4 mg·mL-1, respectively, and the MICs of compound Ⅱ gagainst S. aureus, E. coli, MREC-1# and MREC-2# were 1.6, 3.2, 6.4, 6.4 mg·mL-1, respectively. Its activity on drug-resistant bacteria was better than that of the control drug norfloxacin. CONCLUSION The quinolone derivatives are highly active on drug-resistant bacteria.It is worth of further study.
关键词
喹诺酮 /
磷酸酯 /
微波辐射 /
合成 /
抗菌活性
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Key words
quinolone /
phosphonate /
microwave irradiation /
synthesis /
antibacterial activity
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中图分类号：
R914
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参考文献
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脚注
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基金
贵州省科技厅国际合作项目资助(黔科合外G字[2014]7013);贵州省科技基金项目资助(黔科合J 字LKZ[2010]47);遵义市汇川区科技局资助项目资助(E-123)
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