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.
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