孳生虫源的抗菌化学生物学信息及新型抗生素的发现与构效关系研究

项目名称： 孳生虫源的抗菌化学生物学信息及新型抗生素的发现与构效关系研究

项目编号： No.21472035

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 环境科学、安全科学

项目作者： 尹卫平

作者单位： 河南科技大学

项目金额： 84万元

中文摘要： 近年来，新型感染性疾病的发生及耐药菌的不断出现，成为威胁人类健康的杀手,因此从天然资源中寻找可应对细菌感染的新的抗生素已迫在眉睫。基于前期我们对病媒虫源抗菌活性成分的调查结果，显示其中蝇、蚁和蜚蠊等昆虫的次生代谢物中，含有大量新颖化学结构的天然抗菌物质的信息，可预测新的抗生素的发现。这些孳生昆虫的肆虐生存环境，相信是当前具有产生新型抗生素潜能的不可取代的宝贵资源。本项目以孳生昆虫次生代谢物为研究对象，在对该类虫源抗菌活性成分的系统分离的基础上，重点寻找具广谱抗菌活性的新天然氟化物和抗菌靶标活性分子物质(群)。通过药敏实验的最低抑菌浓度(MIC)测定和对抗病原耐药菌的筛选评价，最终获取新抗生素先导化合物1-2个。进一步探索先导物衍生物的合成和用计算机辅助药物设计进行优化，揭示目标分子的构效关系和抗菌机制。研究不但为新型抗生素的研制提供新途径和新思路，而且丰富了昆虫化学生物学。

中文关键词： 孳生昆虫源；次生代谢物；化学生物学信息；抗菌先导物；构效关系

英文摘要： In recent years, the occurrence of new infectious diseases and multi-drug resistance of bacteria appear constantly, that has become a threat to human health killer. It is thus imminent to look for new antibiotics from the natural resources. Based on previous investigation on the antibacterial compounds of fomite pest source, our results displayed that those secondary metabolites of dirty insects such as fly, ants and blatt contained a lot of natural antibacterial substance with novel chemical structure information, and could predict the discovery of new antibiotics. These insects living in polluted environments are potential and irreplaceable resources of antimicrobials against infectious agents. Selecting the secondary metabolites of polluted insects as the research objects, this project focus on seeking new natural fluoride with broad spectrum antimicrobial activity and antimicrobial target active molecules (group), through the system of separation for producing antimicrobial substances which show insect source potent activity. According to minimun inhibitory concentrations (MIC)determined by agar disk dilution method and multi-drug resistance screening against pathogenic bacteria assay, finally obtain 1-2 new antibiotics lead compounds. It will further reveal the structure-activity relationship and antibacterial mechanism of target molecules by exploring the leads derivatives synthesis and using computer aided drug design optimized. This work will not only provide a new pathway for development of new antibiotics, but also develop the new thinking and enrich the chemical biology of insects study.

英文关键词： Insect living in polluted environments;Secondary metabolites;Chemical biology information;Lead discovery of antibiotics;Structure-activity relationship