含有嘌呤取代查尔酮衍生物设计合成与抗植物病毒活性研究

Crop virus disease prevention and control is a worldwide major problem that has caused many virus variety, wide distribution, serious damage to the crops, significant losses of grain yields. Based on these importance of prevention and control and difficult challenges, our group carried out intensive research on discovering novel antiviral lead structure and agent for plant. Used natural chalcone analogues, three kinds of chalcone derivatives containing purine moiety will been designed and synthesized with purine bioactive groups introduced into targeted molecules. Using half a leaf spot method, the title compounds are tested inhibitory rate to TMV, CMV, target compounds are screened their bioactivities by single tube seedlings method against the south of rice dwarf virus disease (SRBSDV). The EC50 values of antiviral activities against TMV CMV, SRBSDV of active compound will be measured, Combined with computer aided drug molecular design method, CoMFA (or CoMSIA) model will be establishing and the model is provided a practical tool for the modification and optimization of chalcone derivatives containing purine moiety to further improve the antiviral activity. The binding interactions between active small molecules and viruses key protein will be investigated using fluorescence spectroscopy, isothermal titration calorimetry (ITC) and microscale thermophoresis (MST) analysis. The differences in protein, differentially expressed proteins are identified by proteomics technology. The comments, classification and function analysis is confirmed using various bioinformatics. It could further advance the understanding of the action mechanism between antiviral compounds and their target against plant virus.

农作物病毒病防控是一个世界性重大难题，具有病毒种类多、分布范围广、危害作物多、危害损失重的特点。基于防控的重要性与困难的挑战性，本课题以天然产物查尔酮类似物为先导，引入嘌呤类杂环基团，设计与合成三类含嘌呤杂环取代查耳酮衍生物，釆用半叶枯斑法，测试目标化合物抗TMV、CMV病毒活性测试，采用单管单苗法测试测试目标化合物抗南方水稻黑条矮缩病(SRBSDV)的生物活性，并对活性的化合物测定其EC50，结合计算机辅助药物分子设计手段，建立CoMFA（或CoMSIA）模型，指导目标化合物的进一步修饰与改造，以期获得更高活性的抗TMV、CMV、SRBSDV病毒活性的化合物。通过荧光滴定、ITC、MST等方法进行活性小分子与病毒关键蛋白的相互作用的研究，确定活性化合物可能作用机制，采用蛋白质谱技术寻找差异蛋白，利用生物信息学手段对差异表达蛋白质进行注释、分类和功能分析，寻找作用机制。

农作物病毒病防控是一个世界性重大难题，具有病毒种类多、分布范围广、危害作物多、 危害损失重的特点。基于防控的重要性与困难的挑战性，本课题以天然产物查尔酮类似物为先导，引入嘌呤类杂环基团，设计与合成五类含嘌呤杂环取代查耳酮衍生物，釆用半叶枯斑法， 测试目标化合物抗TMV、CMV、PVY病毒活性测试，采用测定番茄褪绿病毒外壳蛋白（ToCV-CP）结合常数，测试目标化合物抗番茄退绿病毒 (ToCV)的生物活性，并对活性的化合物测定其EC50，结合计算机辅助药物分子设计手段，建立CoMFA（或CoMSIA）模型，指导目标化合物的进一步修饰与改造，以期获得更高活性的抗TMV、CMV、ToCV病毒活性的化合物。通过荧光滴定、ITC、MST等方法进行活性小分子 与病毒关键蛋白的相互作用的研究，确定活性化合物可能作用机制，采用蛋白质谱技术寻找差异蛋白，利用生物信息学手段对差异表达蛋白质进行注释、分类和功能分析，寻找作用机制。共合成出 154 个以上新化合物, 发现了2个高活性化合物,活性化合物A5防治番茄病毒病田间小区试验，防效优于对照药剂宁南霉素；发表 SCI收录论文 10 篇；培养硕士研究生 6 名，课题组一名成员获得博士学位；授权国家发明专利3 项；获贵州省科技进步奖一等奖1次。