click反应构建新型具韧皮部输导性和抗蔬菜病毒活性的双功能喹唑啉酮三唑糖苷

There are many kinds of vegetable virus diseases, which are harmful, difficult to prevent and cure, and pose a serious threat to agriculture. Meanwhile, the utilization ratio of the pesticides is low, so it is great significant to seek for antiviral agents with high efficiency, low toxicity and high utilization rate. In this program, the natural product quinazolinone was used as the parent compound and different sugars were used as raw materials. A series of quinazolinone glycosides containing 1,2,3-triazolyl were subtly synthesized via Click Chemistry. The protection and inactivation activities of these compounds against tobacco mosaic virus, cucumber mosaic virus and potato Y virus were tested by in vivo, and the relationship between antivirus activity and structure was also studied. A 3D-QSAR model was constructed to optimize structures in order to design more active antiviral compounds. On the basis of high antivirus activity, phloem mobility were carried out in order to obtain the compounds with high utilization ratio. The successful development of the project can provide a new structure with efficient, low toxic and environmentally friendly antiviral agents for vegetables, provide a new idea for improving the utilization rate of pesticides and help to find the leading structure of anti-vegetable virus agents with higher activity.

蔬菜病毒病害种类多，危害大，防治困难，对农业造成严重威胁，且防治药剂利用率低，因此寻求高效、低毒和利用率高的的抗病毒药剂具有重要意义。本申请课题采用活性亚结构拼接策略，以天然产物喹唑啉酮为母体与不同糖为原料，经“点击”反应，巧妙合成系列结构新颖的、具有韧皮部输导性和抗蔬菜病毒活性的双功能喹唑啉酮三唑糖苷化合物，并测试其对3种蔬菜病毒TMV、CMV和PVY的保护、钝化活性。结合活性与结构关系，构建3D-QSAR模型，优化设计与合成更高活性的抗病毒化合物。在高活性化合物基础上，开展有助于提高农药利用率的韧皮部输导性研究。申请项目的成功开展为高效、低毒、环境友好的抗蔬菜病毒药剂研发提供新结构，为提高农药利用率的研究提供新思路，有助于发现具有更高活性抗蔬菜病毒病药剂的先导结构。

蔬菜病毒病害种类多，危害大，防治困难，对农业造成严重威胁，且防治药剂利用率低，因此寻求高效、低毒和利用率高的的抗病毒药剂具有重要意义。本项目采用糖基为导向基团，喹唑啉酮为抗病毒活性片段，经“点击”化学将其偶联，构建了系列喹唑啉酮-三唑-糖基偶合物84个，经核磁共振、高分辨质谱对其进行结构表征。通过半叶枯斑法，对偶合物抗病毒活性进行初筛，筛选出对TMV具有良好治疗活性和保护活性的偶合物Glu-a16，与商品化的对照药剂宁南霉素的保护活性和治疗活性相当。探究了偶合物的构效关系：整体趋势单糖偶合物的抗病毒活性优于二糖偶合物的抗病毒活性；脱保护的偶合物的抗病毒活性优于全乙酰化化合物的抗病毒活性；苯环上有F-、Cl-吸电子基团取代时，抗病毒活性会提高。通过韧皮部渗出液筛选法，筛选出的高活性偶合物Glu-a16，兼具韧皮部输导活性。而偶合物Glu-a16的母体喹唑啉酮无韧皮部输导性，表明糖基可改善化合物韧皮部输导性。初步探究了偶合物Glu-a16其抗病毒机制，表明该偶合物处理会提高防御酶（苯丙氨酸解氨酶(PAL)、超氧化物歧化酶(SOD)、过氧化物酶(POD)、多酚氧化酶(PPO)）的活性，从而进一步提高其抗病性，从而使烟草对TMV侵染具有一定的防效。兼具韧皮部输导性和抗病性化合物双功能小分子偶合物的成功构建，可为后期研发防控维管病害的农药提供借鉴。

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