硝唑尼特衍生物的合成及其抑菌活性研究  

Study on the Synthesis of Nitazoxanide Derivatives and Their Antibacterial Activities

作　　者：王满梅 王艳平 刘迎春[2] 王春梅[2] 黄振 王霄旸[2] 张可煜[2] 李娟 WANG Manmei;WANG Yanping;LIU Yingchun;WANG Chunmei;Huang Zhen;WANG Xiaoyang;ZHANG Keyu;LI Juan(College of Chemistry,Xiangtan University,Xiangtan 411100,China;Key Laboratory of Veterinary Chemical Drugs and Pharmaceutics,Ministry of Agriculture and Rural Affairs,Shanghai Veterinary Research Institute,CAAS,Shanghai 200241,China)

机构地区：[1]湘潭大学化学学院,湘潭411100 [2]中国农业科学院上海兽医研究所农业农村部兽用化学药物及制剂学重点实验室,上海200241

出　　处：《中国动物传染病学报》2022年第3期71-78,共8页Chinese Journal of Animal Infectious Diseases

基　　金：国家自然科学基金(31872516);国家重点研发计划(2018YFE0192600)。

摘　　要：硝唑尼特具有广泛的生物活性,为进一步挖掘硝唑尼特的抗菌潜力,本研究通过亲核取代反应合成系列硝唑尼特衍生物,完成目标产物的结构分析和鉴定。通过采用微量肉汤稀释法测定硝唑尼特、硝唑尼特衍生物、已上市抗菌药物对大肠杆菌、金黄色葡萄球菌等6种细菌的最低抑菌浓度和最低杀菌浓度,监测衍生物a对细菌的抑制生长曲线。结果显示,衍生物a对测试细菌具有较好的抑菌活性,抑菌效果优于母药硝唑尼特及替唑尼特,其中对蜡样芽孢杆菌和金黄色葡萄球菌等菌株的MIC值达1μg/mL,抑菌效果强于美罗培南、亚胺培南和多粘菌素B。此外,衍生物a对蜡样芽孢杆菌和金黄色葡萄球菌的生长繁殖也有很好的抑制作用,显示出继续开发的潜力。Nitazoxanide has a wide range of biological activities.In order to further explore the potential antibacterial activities,a series of nitazoxanide derivatives were synthesized by nucleophilic substitution reaction and their structures and target products were analyzed in the present.Then,the minimum inhibitory and bactericidal concentrations of nitazoxanide,nitazoxanide derivatives and marketed antibacterial drugs were determined by using micro-broth dilution method and 6 species of bacteria such as Escherichia coli and Staphylococcus aureus.monitor the derivative a growth inhibition curve for bacteria.The results show that the derivative a had good antibacterial activity against the tested bacteria with superior to its parent drugs nitazoxanide and tizoxanide.The minimum inhibitory concentration was 1μg/mL for Bacillus cereus and Staphylococcus aureus.Overall,the derivative a showed stronger bacteriostatic effect than meropenem,imipenem and polymyxin B,indicating a potential market value.

关 键 词：硝唑尼特 衍生物 抑菌活性 耐药性 

分 类 号：S859.5[农业科学—临床兽医学]