聚乙炔化合物的合成、抑菌活性及机理研究

Fusarium pseudograminearum is one of the most serious pathogens in wheat production, which mainly causes root rot disease of cereal crops, and causes food safety problems of toxin infection. At present, there is no effective fungicide to control it. Discovering lead compounds from natural products, exploring the action mechanism and the target of compounds, and rational designing and synthesizing novel inhibitors based on new targets, is one of the most important strategies for discovering novel pesticides. In the roots of the genus Umbelliferae plants, the natural polyacetylene compounds with structural diversity are used to prevent the pests and diseases in the soil. In this study, we are intending to synthesize the polyacetylene compounds with structural diversity in the roots of Umbelliferae plants, and studying the bioactivity against soil-borne fungal diseases Fusarium pseudograminearum. The quantitative structure-activity relationship would be studied and the structure of the structure of compounds will be optimized for new efficient and low-toxic fungicides. At the same time, the proteomics technology will be used to explore the anti-fungi mechanism of the polyacetylene compounds and the related metabolic pathway. This study will provide a theoretical and practical basis for further exploration of new targets of Fusarium pseudograminearum and the development of new botanical ungicides based on rational design.

假禾谷镰刀菌是国内危害小麦生产最主要的病原菌之一，主要引起谷类作物的根腐病害，并造成毒素感染的食品安全问题，目前缺乏有效的防控技术手段。从天然产物中寻找先导化合物，探索药物的作用机理及作用靶标，从而基于有害生物新靶标进行合理设计与合成修饰，是新农药创制的主要途径之一。在伞形科植物的根部表皮中，具有结构多样性的聚乙炔天然产物，主要用于防止土壤中病虫害侵染作物根部。本课题拟合成伞形科植物根部中的多样性聚乙炔化合物，以假禾谷镰刀菌为对象，进行土传真菌病害的抑菌生物活性测定，在此基础上通过定量构效关系研究和化合物结构优化，力求开发更加高效、低毒的杀菌活性先导化合物；同时本课题拟利用蛋白质组学技术探索聚乙炔化合物的抑菌作用机理和相关的生化代谢途径。该研究将为进一步探索假禾谷镰刀菌土传病害新作用靶标，开展基于有害生物新靶标进行合理设计，以及新型植物源杀菌剂的开发，提供相关理论依据和实践基础。

假禾谷镰刀菌是国内危害小麦生产最主要的病原菌之一，主要引起谷类作物的根腐病害，并造成毒素感染的食品安全问题，目前缺乏有效的防控技术手段。在伞形科植物的根部表皮中，具有结构多样性的聚乙炔天然产物，主要用于防止土壤中病虫害侵染作物根部。本项目通过合成伞形科植物根部中的多样性聚乙炔化合物，以假禾谷镰刀菌等病原菌为对象，进行土传真菌病害的抑菌生物活性测定，在此基础上通过定量构效关系研究和化合物结构优化，开发出更加高效、低毒的杀菌活性先导化合物，EC50 = 0.98 - 8μg/mL；同时本课题利用蛋白质组学技术探索聚乙炔化合物的抑菌作用机理和相关的生化代谢途径，确定了药物的杀菌作用机制与糖酵解与氧化磷酸化途径相关，初步分析推测化合物的靶标可能与线粒体内膜蛋白或线粒体内的激酶有关。该研究将为进一步探索假禾谷镰刀菌土传病害新作用靶标，开展基于有害生物新靶标进行合理设计，以及新型植物源杀菌剂的开发，提供相关理论依据和实践基础。