基于抗菌氟喹诺酮的作用靶拓扑异构酶与哺乳动物的相似性,为寻找由抗菌活性到抗肿瘤活性转化的有效修饰方法,用(噁)二唑杂环作为诺氟沙星(1)的羧基电子等排体得中间体,1-乙基-6-氟-7-(哌嗪-1-基)-3-(5-巯基-1,3,4-(噁)二唑-2-基)-喹啉-4(1H)-酮(3),化合物3与氯甲基(噁)二唑(4a ～4e)进行S-醚化得双(噁)二唑甲硫醚(5a～5e),再进一步甲基化和季铵化得相应的N-甲基双(噁)二唑甲硫醚(6a～6e)和N,N-二甲基双(噁)二唑甲硫醚碘化物(7a～7e).双(噁)二唑甲硫醚目标物的结构经元素分析、1 H NMR、MS技术确证.采用MTT 法评价了目标化合物对体外培养人肝癌细胞株Hep-3B生长的抑制活性.结果表明,15个目标化合物的抑制活性均显著高于对照化合物1的抑制活性,其季铵盐的IC50值低于25.0 μmol/L,显示出潜在的抗癌活性.
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