Guo Xin, Zhang Peiyao, Chen Miaomiao, Li Taiqing, Hou Cancan, Que Xinyue, Xu Li, Zhou Zhenghong, Wang Qingmin, Wang Ziwen
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.
Bioorg Chem. 2024 Dec;153:107757. doi: 10.1016/j.bioorg.2024.107757. Epub 2024 Aug 29.
Diseases caused by plant viruses and pathogens pose a serious threat to crop yield and quality. Traditional pesticides have gradually developed drug resistance and brought certain environmental safety issues during long-term overuse. There is an urgent need to discover new candidate compounds to address these issues. In this study, we achieved the efficient synthesis of iheyamine A and its derivatives, and discovered their excellent antiviral activities against tobacco mosaic virus (TMV). Most compounds displayed higher antiviral activities against TMV than commercial ribavirin at 500 μg/mL, with compounds 3a (Inactive effect IC: 162 µg/mL), 3d (Inactive effect IC: 249 µg/mL), 6p (Inactive effect IC: 254 µg/mL), and 7a (Inactive effect IC: 234 µg/mL) exhibiting better antiviral activities than ningnanmycin at 500 μg/mL (Inactive effect IC: 269 µg/mL). Meanwhile, the structure-activity relationships of this type of compounds were systematically studied. We chose 3a for further antiviral mechanism research and found that it can directly act on viral coat protein (CP). The interaction of 3a and CP was further verified via molecular docking. These compounds also showed broad-spectrum fungicidal activities against 8 plant pathogenic fungi, especially for P. piricola. This study provides a reference for the role of iheyamine alkaloids in combating plant pathogenic diseases.
由植物病毒和病原体引起的疾病对作物产量和质量构成严重威胁。传统农药在长期过度使用过程中逐渐产生抗药性，并带来了一定的环境安全问题。迫切需要发现新的候选化合物来解决这些问题。在本研究中，我们实现了艾海胺A及其衍生物的高效合成，并发现它们对烟草花叶病毒（TMV）具有优异的抗病毒活性。在500μg/mL时，大多数化合物对TMV的抗病毒活性高于市售利巴韦林，其中化合物3a（抑制中浓度IC：162μg/mL）、3d（抑制中浓度IC：249μg/mL）、6p（抑制中浓度IC：254μg/mL）和7a（抑制中浓度IC：234μg/mL）在500μg/mL时表现出比宁南霉素（抑制中浓度IC：269μg/mL）更好的抗病毒活性。同时，系统研究了这类化合物的构效关系。我们选择3a进行进一步的抗病毒机制研究，发现它可以直接作用于病毒外壳蛋白（CP）。通过分子对接进一步验证了3a与CP的相互作用。这些化合物对8种植物病原真菌也表现出广谱杀菌活性，尤其是对梨火疫病菌。本研究为艾海胺生物碱在防治植物病原病害中的作用提供了参考。
