基于本研究组建立的活性天然产物发现及结构优化规律模型和前期发现氮杂卓并吲哚类新化合物具有很好的抗植物病毒活性，本项目拟对上述hymenialdisine类海洋生物碱开展系统研究：发展高效构筑吡咯并氮杂卓骨架方法，实现系列hymenialdisine类生物碱的合成；基于骨架迁越、氢键作用的药物设计理念对hymenialdisine类生物碱进行结构多样性衍生，改善天然产物生物活性和成药性；研究目标化合物抗植物病毒活性和构效关系，寻找药效团，进一步指导分子设计；进行活性分子的稳定性、溶解性和logP值等理化性质研究；对优选的化合物进行急性经口毒性及田间小区试验；结合分子理化性质、毒性、室内和田间防效进一步优化分子结构，发现高效候选品种；运用电镜、荧光滴定、活性氧测定以及光亲和探针技术对高效候选品种进行作用机制初步探索。最终期望创制出具有我国自主知识产权、符合生态农药要求的高效植物病毒病防治药剂。

Based on the bioactive natural products discovery and structural optimization law model established by our research group, and the discovery that new diazepinoindole compounds exhibit highly antiviral activity, this project intends to systematically study hymenialdisine alkaloids: Efficient methods for the construction of pyrrolo[2,3-c]azepine skeletons and the synthesis of hymenialdisine alkaloids will be developed. Based on the drug design concept of scaffold hopping and hydrogen bonding, these hymenialdisine alkaloids will be derived to improve their biological activity and druggability. The activity and SARs of the target compounds against plant viruses will be studied to search for pharmacophore, which will further guide the molecular design. The physicochemical properties of the active molecules, such as stability, solubility and logP value, etc. will also be studied. Acute oral toxicity test and field plot test of the selected compounds will be performed. The molecular structure will be further optimized by comprehensive considering the molecular physicochemical properties, toxicity, indoor and field efficacy. Using electron microscopy, fluorescence titration, ROS detection and PAL technology, the mode of action of the highly effective candidate drugs will be preliminarily explored. Finally, it is expected to create efficient plant viral disease control agents with independent intellectual property rights that meet the requirements of ecological pesticides.