氮杂环修饰的甲硝唑配合物的设计、合成及抗幽门螺旋杆菌活性研究

项目名称： 氮杂环修饰的甲硝唑配合物的设计、合成及抗幽门螺旋杆菌活性研究

项目编号： No.21301108

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 数理科学和化学

项目作者： 秦洁

作者单位： 山东理工大学

项目金额： 24万元

中文摘要： 以药物分子为配体的配合物兼具药物活性分子和金属离子的特性，两者间的协同效应可以克服药物分子在临床使用时存在的副作用和耐药性等问题，因此药物配合物在新型药物筛选中具有广泛的应用前景。脲酶是幽门螺旋杆菌的重要致病因子，通过对传统的脲酶抑制剂进行修饰，进而制备、筛选药物配合物型脲酶抑制剂作为抑制幽门螺旋杆菌的药物是一种很好的抑菌策略。本课题以抗幽门螺旋杆菌代表药物甲硝唑为母体，设计并合成系列基于氮杂环修饰的甲硝唑衍生物的过渡金属配合物。通过对所合成的配合物进行体外抑制脲酶活性、抗幽门螺旋杆菌活性及计算机模拟对接分析，研究此类脲酶抑制剂的构效关系，为筛选具有高效脲酶抑制活性的先导配合物研究奠定实验和理论基础。本项目的实施，有望将配合物引入抗幽门螺旋杆菌药物的研究，开拓抗幽门螺旋杆菌药物化学的研究思路。

中文关键词： 生物功能配合物；氮杂环；脲酶抑制；抗菌活性；分子对接

英文摘要： Coordination compounds based on biologically active ligands have prospective applications in new drug screening since they have both the characteristics of pharmaceutically active molecules and metal ions, between which, even more importantly, the synergistic effect can overcome the side effects and drug resistance in clinical use. Urease is the important pathogenic factor of Helicobacter pylori. By modifying the traditional urease inhibitor, we can prepare and screening coordination complex. It's a good antibacterial strategy to use the complex as urease inhibitor for inhibition of the Helicobacter pylori. With those in mind, this project focus on the bioactive metal complexes based on metronidazole-nitrogenous heterocycle derivatives as urease inhibitor for inhibition of the Helicobacter pylori. The aim is to analyze the structure-activity relationship of those complexes by biological evaluation and computer-aided molecular docking, to screening highly active precursors of urease inhibitors, which can establishe the experimental and theoretical foundation for the feasibility of coordination compounds acting as urease inhibitors. Based on that, we can explore the potential application of bioactive metal complexes as anti-Helicobacter pylori drugs, opening new research idea in anti-Helicobacter pylori drug desig

英文关键词： bioactive complex；N-based heterocycle；urease inhibition；antibacterial activity；molecular docking