基于飞蝗基因组学靶向多巴胺受体的农药先导化合物的发现及其结构活性关系研究

The molecular target-oriented design of pesticide molecules is an important development direction of the new pesticide innovation today. Based on the major breakthrough in the locust genome and molecular mechanisms of phase change in locusts, a new "genome to lead" approach for insecticide discovery will be used to find high-efficient and low-toxic pesticide lead compounds interfering with the gregarious behavior of locusts. Furthermore, the gradually in-depth structural optimization of pesticide lead compounds will be expected to find a highly type-specific and ultra-highly effective pesticide with insect behavior regulation features. In a word, this project will provide a new idea and strategy to prevent the outbreak of the locust plague, at the same time，it has important theoretical and practical significance for the discovery of pesticide lead compounds targeted dopamine receptors in locusts and the maintenance of ecosystem balance (especially grassland ecosystem).

分子靶标导向的农药分子设计是当前新农药创制的重要发展方向。本项目基于飞蝗全基因组图谱及飞蝗型变分子机制研究的重大突破，拟运用"基因组学-先导（genome to lead）"的杀虫剂筛选新方法寻找高效、低毒、干扰飞蝗群居行为的农药先导结构，进一步对农药先导进行分子结构优化，期望创制出高选择性、超高效、调控为特征的绿色新农药品种，同时建立"基因组学－靶标基因－高通量筛选－先导－候选农药－农药品种"的绿色新农药创制技术平台。总之，本项目为防止蝗灾爆发提供新的思路和策略，对于发现靶向飞蝗多巴胺受体的农药先导结构和维护生态系统（特别是草原生态系统）平衡具有重要的理论和现实意义。

分子靶标导向的农药分子设计是当前新农药创制的重要发展方向。本项目基于飞蝗全基因组图谱及飞蝗型变分子机制研究的重大突破，建立了“基因组学-先导（genome to lead）”的杀虫剂筛选新方法，设计合成了5类共计139个化合物，意外发现了一个对库蚊幼虫具有高活性并且对斑马鱼低毒的化合物，同时发现了2个骨架结构新颖、具有广谱抗真菌活性的高活性化合物。本项目发表SCI论文4篇，申请中国发明专利2项。培养硕士研究生5名，其中2名已取得硕士学位。