基于天然产物瑞香狼毒活性成分的新农药先导发现研究

项目名称： 基于天然产物瑞香狼毒活性成分的新农药先导发现研究

项目编号： No.21272266

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 数理科学和化学

项目作者： 凌云

作者单位： 中国农业大学

项目金额： 80万元

中文摘要： 从天然产物发现结构新颖、对环境安全的农药是一条重要且高效的途径。(E)-1,5-二苯基-2-烯-1-戊酮 (I)是我国特有的植物瑞香狼毒中的化学成分之一，已有研究表明该化合物结构简单并具有良好的杀虫活性，可以作为农药先导进行进一步研究。本项目在前期研究基础之上，依据电子等排原理及活性亚结构拼接法等分子设计方法，以I为先导设计了四大类六小类含有活性杂环、天然黄酮、香豆素类似片段的新型结构；拟通过有机合成技术制备目标化合物并对它们进行杀菌和杀虫生物活性评价，在此基础上，进一步探索化合物结构与活性之间的关系，提出具有预测功能的QSAR模型，指导进一步的优化设计研究。通过上述基于化学、生物及计算机技术等手段的系统优化研究，期望高效率地发现具有优于先导活性的新型候选化合物。本项目基于天然源活性物质发现新颖农药先导的研究，对绿色新农药的开发具有十分重要的意义。

中文关键词： 瑞香狼毒；先导发现；生物活性；构效关系；

英文摘要： Natural product is a key and efficient way to discover pesticide with novel structure, low risk to environment. (E)-1,5-Diphenyl-2-penten-1-one (I), one of natural compounds separated from a specific plant in China, Stellera chamaejesme L, was proved to be a lead compound with simple structure, good insecticidal and fungicidal activity in previous work. In this project, based on our previous results, four types containing six series analogues of lead compound I are designed with the structural modification strategy of bioisosterism and linking active sub-structures such as heterocycle, flavone and coumarin fragments etc. The target compounds will be obtained via organic synthesis and their activity will be evaluated with bioassay both for insecticide and fungicide. Followed the study of the relationship between their structures and activities, a prediction QSAR model will be proposed for further optimization. Some new candidate compounds with higher pesticide activity should be discovered efficiently after the above systemic study with comprehensive techniques of chemistry, biology and computation chemistry. This project is a useful attempt to find novel structures based on natural products and its result will exhibit an important significance for green pesticide discovery.

英文关键词： Stellera chamaejesme L；Lead Discovery；Organic Synthesis；Biological Activity；QSAR