Ji Xiaofei, Guo Jincheng, Liu Yuxiu, Lu Aidang, Wang Ziwen, Li Yongqiang, Yang Shaoxiang, Wang Qingmin
State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, College of Chemistry, Collaborative Innovation Center of Chemical Science and Engineering , Nankai University , Tianjin 300071 , China.
Tianjin Key Laboratory of Structure and Performance for Functional Molecules, Key Laboratory of Inorganic-Organic Hybrid Functional Materials Chemistry, Ministry of Education, College of Chemistry , Tianjin Normal University , Tianjin 300387 , China.
J Agric Food Chem. 2018 Apr 25;66(16):4062-4072. doi: 10.1021/acs.jafc.8b00507. Epub 2018 Apr 9.
Nortopsentin alkaloids were found to have potent antiviral, anti-phytopathogenic-fungus, and insecticidal activities for the first time. Antiviral-activity tests revealed that these compounds were very sensitive to substituents, so a series of nortopsentin derivatives were designed, synthesized, and systematically evaluated for their antiviral activities against TMV, their fungicidal activities, and their insecticidal activities on the basis of a structural-diversity-derivation strategy. Compounds 2e (in vivo inactivation-, curative-, and protective-activity inhibitory rates of 50, 59, and 56%, respectively, at 500 μg/mL) and 2k (in vivo inactivation-, curative-, and protective-activity inhibitory rates of 60, 58, and 52%, respectively, at 500 μg/mL), with excellent antiviral activities and good physicochemical properties, emerged as new lead compounds for novel-antiviral-agent development. Further fungicidal-activity tests revealed that these alkaloids displayed broad-spectrum fungicidal activities. Compounds 2f, 2h, and 2j emerged as new lead compounds for antifungal-activity research. Additionally, all the compounds displayed good insecticidal activities against five kinds of insects, including Mythimna separate, Helicoverpa armigera, Ostrinia nubilalis, Plutella xylostella, and Culex pipiens pallens.
首次发现诺托品生物碱具有强大的抗病毒、抗植物病原真菌和杀虫活性。抗病毒活性测试表明，这些化合物对取代基非常敏感，因此基于结构多样性衍生策略，设计、合成并系统评估了一系列诺托品衍生物对烟草花叶病毒（TMV）的抗病毒活性、杀菌活性和杀虫活性。化合物2e（在500μg/mL时，体内灭活、治疗和保护活性抑制率分别为50%、59%和56%）和2k（在500μg/mL时，体内灭活、治疗和保护活性抑制率分别为60%、58%和52%），具有优异的抗病毒活性和良好的理化性质，成为新型抗病毒药物开发的新先导化合物。进一步的杀菌活性测试表明，这些生物碱具有广谱杀菌活性。化合物2f、2h和2j成为抗真菌活性研究的新先导化合物。此外，所有化合物对五种昆虫均表现出良好的杀虫活性，包括粘虫、棉铃虫、玉米螟、小菜蛾和淡色库蚊。
