Marine Natural Product for Pesticide Candidate: Pulmonarin Alkaloids as Novel Antiviral and Anti-Phytopathogenic-Fungus Agents

Plant diseases are seriously endangering agricultural production. The emergence of drug resistance has brought great challenges to the prevention and control of plant diseases. There is an urgent need for the emergence of new drug candidates. In this work, we achieved the efficient synthesis of pulmonarins A and B in 64% and 59% overall yield, respectively. Pulmonarins A and B were found to have good antiviral activities against tobacco mosaic virus (TMV) for the first time. A series of pulmonarin derivatives were designed, synthesized, and evaluated for their antiviral and fungicidal activities systematically. Most compounds displayed higher anti-TMV activities than commercial ribavirin. Compounds 6a, 6c, and 6n with better inactivation effects than ningnanmycin emerged as new antiviral candidates. We selected 6c for further antiviral mechanism research, which revealed that it could inhibit virus assembly by interacting with TMV coat protein (CP). The molecular docking results further confirmed that these compounds could interact with CP through hydrogen bonding. These compounds also displayed broad spectrum fungicidal activities. Especially compound 6u with prominent antifungal activity emerged as a new fungicidal candidate for further research. The current work provides a reference for understanding the application of pulmonarin alkaloids in plant protection.