Tianjin Key Laboratory of Structure and Performance for Functional Molecules, College of Chemistry, Tianjin Normal University, Tianjin 300387, 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. 2020 Oct 14;68(41):11350-11357. doi: 10.1021/acs.jafc.0c04868. Epub 2020 Sep 30.
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 , , and with better inactivation effects than ningnanmycin emerged as new antiviral candidates. We selected 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 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.
植物病害严重威胁农业生产。抗药性的出现给植物病害的防治带来了巨大的挑战。迫切需要新的药物候选物的出现。在这项工作中，我们分别以 64%和 59%的总收率高效合成了 pulmonarins A 和 B。首次发现 pulmonarins A 和 B 对烟草花叶病毒 (TMV) 具有良好的抗病毒活性。我们系统地设计、合成并评估了一系列 pulmonarin 衍生物的抗病毒和杀菌活性。大多数化合物的抗 TMV 活性均高于商业利巴韦林。化合物 、 和 比宁南霉素具有更好的失活作用，成为新的抗病毒候选物。我们选择 进行进一步的抗病毒机制研究，结果表明它可以通过与 TMV 外壳蛋白 (CP) 相互作用抑制病毒组装。分子对接结果进一步证实这些化合物可以通过氢键与 CP 相互作用。这些化合物还表现出广谱杀菌活性。特别是化合物 具有突出的抗真菌活性，有望成为进一步研究的新型杀真菌候选物。本研究为了解 pulmonarin 生物碱在植物保护中的应用提供了参考。
