硝基咪唑类衍生物的合成及其抗菌活性研究  

Synthesis and antibacterial activity of nitroimidazole derivatives

作　　者：程敬东 王合珍 王京 罗远纯 张磊 Cheng Jingdong;Wang Hezhen;Wang Jing;Luo Yuanchun;Zhang Lei(Key Laboratory of Biocatalysis&Chiral Drug Synthesis of Guizhou Province,School of Pharmacy,Zunyi Medical University,Zunyi Guizhou 563099,China;Pharmaceutical and Cosmetics Department,Zunyi Product Quality Inspection and Testing Institute,Zunyi Guizhou 563002,China)

机构地区：[1]遵义医科大学贵州省生物催化与手性药物合成重点实验室,药学院,贵州遵义563099 [2]遵义市产品质量检验检测院药品化妆品部,贵州遵义563002

出　　处：《遵义医科大学学报》2023年第2期145-151,共7页Journal of Zunyi Medical University

基　　金：遵义市科学技术局重点学科(创新团队)建设项目(NO:[2020]293)。

摘　　要：目的通过化学合成一系列新型硝基咪唑类衍生物,并对其进行体外抑菌活性测试。方法以甲硝唑、奥硝唑、塞克硝唑等硝基咪唑药物为原料,与喹啉类化合物5-氯-8-羟基喹啉通过取代反应、醚化反应等方法,得到一类新型的硝基咪唑类衍生物,其结构经1H NMR,13C NMR和高分辨质谱分析确证,并对目标化合物进行抗菌活性筛选。结果大部分化合物对于金黄色葡萄球菌具有较好的抗菌活性。其中,化合物5活性最强,对金黄色葡萄球菌的最小抑制浓度为0.59μmol;化合物6对金黄色葡萄球菌和耐甲氧西林金黄色葡萄球菌都具有抑制活性,最小抑制浓度均为2.39μmol。结论将5-氯-8-羟基喹啉作为药效基团引入硝基咪唑类药物分子的结构中,有利于提高硝基咪唑类药物的抗金黄色葡萄球菌活性,为后续硝基咪唑衍生物的研究提供了一定的实验基础。Objective A series of novel nitroimidazole derivatives were synthesized and tested for their antibacterial activity in vitro.Methods By using nitroimidazoles(metronidazole,ornidazole and secnidazole)and 5-chloro-8-quinolinol as starting materials.The structures of synthesized compounds were confirmed by~1H NMR,13C NMR and HR-MS.The compounds were then screened for antibacterial activity.Results The results showed that most of the target compounds had good antibacterial activity against Staphylococcus aureus.Among them,compound 5 had the best activity against Staphylococcus aureus with the minimum inhibitory concentration(MIC)value of 0.59μmol,and compound 6 had the same effective activity on Staphylococcus aureus and methicillin-resistant Staphylococcus aureus,with the MIC value of 2.39μmol.Conclusion Introducing the pharmacophore of 5-chloro-8-hydroxyquinoline into the nitroimidazole structures improves the antibacterial activity against Staphylococcus aureus,which provides a certain experimental basis for the research on the antibacterial activity of nitroimidazole derivatives.

关 键 词：硝基咪唑 5-氯-8-羟基喹啉 衍生物合成 抗菌活性 

分 类 号：O625.8[理学—有机化学]