School of Chemical Engineering and Technology, Hebei University of Technology, Tianjin 300130, China.
State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, College of Chemistry, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin 300071, China.
J Agric Food Chem. 2021 Sep 8;69(35):10093-10103. doi: 10.1021/acs.jafc.1c04098. Epub 2021 Aug 27.
With the increasing severity of plant diseases and the emergence of pathogen resistance, there is an urgent need for the development of new efficient and environment-friendly pesticides. Marine natural product (MNP) resources are rich and diverse. Structural simplification based on MNPs is an important strategy to find novel pesticide candidates. In this work, the marine natural product 6″-debromohamacanthin A () was efficiently prepared and selected as the parent structure. A series of hamacanthin derivatives were designed, synthesized, and studied on the antiviral and antifungal activities. Most of these compounds displayed higher antiviral activities than ribavirin. The antiviral activities of compounds and - are similar to or higher than that of ningnanmycin (perhaps the most efficient anti-plant-virus agent). Compound was selected for further antiviral mechanism research via transmission electron microscopy, molecular docking, and fluorescence titration. The results showed that compound could bind to TMV CP and interfere with the assembly process of TMV CP and RNA. In addition, these hamacanthin derivatives also exhibited broad-spectrum inhibitory effects against eight common agricultural pathogens. Compounds , , and with excellent fungicidal activities can be considered as new fungicidal candidates for further research. These results provide a basis for the application of hamacanthin alkaloids in crop protection.
随着植物病害的日益严重和病原体抗性的出现，迫切需要开发新的高效环保农药。海洋天然产物（MNP）资源丰富多样。基于 MNPs 的结构简化是寻找新型农药候选物的重要策略。在这项工作中，高效制备了海洋天然产物 6″-去溴哈马卡汀 A（），并选择其作为母体结构。设计、合成了一系列哈马卡汀衍生物，并研究了它们的抗病毒和抗真菌活性。这些化合物中的大多数表现出比利巴韦林更高的抗病毒活性。化合物和的抗病毒活性与宁南霉素（可能是最有效的抗病毒剂）相似或更高。通过透射电子显微镜、分子对接和荧光滴定，选择化合物进一步研究其抗病毒机制。结果表明，化合物可以与 TMV CP 结合，并干扰 TMV CP 和 RNA 的组装过程。此外，这些哈马卡汀衍生物还对八种常见农业病原体表现出广谱抑制作用。具有优异杀菌活性的化合物、和可被视为进一步研究的新型杀菌候选物。这些结果为哈马卡汀生物碱在作物保护中的应用提供了依据。
