新型莫西沙星衍生物的合成及其抑菌活性

Synthesis and Bacteriostatic Activities of Novel Moxifloxacin Derivatives

合成了一系列新的含有潜在多活性官能团的新型莫西沙星衍生物,对药物的筛选和制药行业具有重要的应用价值。以莫西沙星为原料,在无催化剂室温反应条件下,与3-甲酸色酮发生Michael加成,然后脱羧开环反应,获得了8个新型莫西沙星衍生物 3a ~ 3h ,产率72%~85%,其结构经 ^(1)H NMR, ^(13)C NMR和 HR-MS (ESI-TOF)表征。该类化合物在莫西沙星骨架上拼接了活性基团水杨酮烯烃,可以为生物活性筛选提供物质基础。采用抑菌圈实验研究了衍生物 3a ~ 3h 的抑菌活性,采用MBC(最低杀菌浓度)和MIC(最低抑菌浓度)实验进一步研究了衍生物 3e 的抑菌活性。结果表明:莫西沙星衍生物 3a ~ 3h 显示了很好的抑菌活性,其中衍生物 3e 的抑菌效果接近阳性对照药莫西沙星,对金黄色葡萄球菌表现出显著的抑制效果。MBC和MIC测试的实验结果 表明 :衍生物 3e 对菌株的抑制效果优于阳性对照药链霉素。

The synthesis of a series of new moxifloxacin derivatives with potential multiple functional groups has important application value for drug screening and pharmaceutical industry.In this paper,the Michael addition and then decarboxylation/ring opening reaction of moxifloxacin with chromone 3-carboxylates was investigated at room temperature without catalyst,to provide a variety of novel moxifloxacin derivatives(3a~3h)in 72%~85%yields.The structures of products 3 were characterized by ^(1)H NMR,^(13)C NMR and HR-MS(ESI-TOF).The antibacterial activity of moxifloxacin derivatives 3a~3h was studied by bacteriostatic ring experiment,and the antibacterial activity of derivative 3e was further studied by MBC(minimum bactericidal concentration)and MIC(minimal inhibitory concentration)experiments.The results showed that these derivatives 3a~3h showed good antibacterial activity,and the antibacterial effect of the derivative 3e was close to that of the positive control drug moxifloxacin,and showed significant antibacterial effect on staphylococcus aureus.MBC and MIC experiments showed that the inhibitory effect of derivative 3e on bacteria was better than that of positive control drug streptomycin.