海洋天然产物用于药物发现：新型抗病毒和抗植物病原真菌剂——凯立宁 A-C 及其衍生物的首次发现。
Marine Natural Products for Drug Discovery: First Discovery of Kealiinines A-C and Their Derivatives as Novel Antiviral and Antiphytopathogenic Fungus Agents.
机构信息
Tianjin Key Laboratory of Structure and Performance for Functional Molecules, Key Laboratory of Inorganic-Organic Hybrid Functional Materials Chemistry (Tianjin Normal University), Ministry of Education, 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.
出版信息
J Agric Food Chem. 2018 Jul 18;66(28):7310-7318. doi: 10.1021/acs.jafc.8b02238. Epub 2018 Jul 5.
Leucetta alkaloid kealiinines A-C and kealiinine B derivatives were designed, synthesized, and characterized on the basis of NMR and HR-MS. The anti-TMV and antiphytopathogenic fungus activities of these alkaloids were evaluated for the first time. Kealiinine B exhibited a higher anti-TMV activity than kealiinines A and C. Kealiinine B derivatives 2m (inhibitory rates: 68, 66, and 71% at 500 μg/mL for inactivation, curative, and protection activity in vivo, respectively) and 2y (inhibitory rates: 69, 64, and 63% at 500 μg/mL for inactivation, curative, and protection activity in vivo, respectively) showed significantly higher antiviral activity than ningnanmycin (inhibitory rates: 56, 56, and 58% at 500 μg/mL for inactivation, curative, and protection activity in vivo, respectively), thus emerging as new lead compounds for novel antiviral agent development. Structure-activity relationship research provided the basis for structural simplification of these alkaloids. Further fungicidal activity tests revealed that these alkaloids displayed broad-spectrum fungicidal activities. Compounds 2i and 2p displayed good fungicidal activities in vitro against Sclerotinia sclerotiorum and Rhizoctonia cerealis with inhibition rates of 71%/50 mg/kg and 70%/50 mg/kg, respectively.
基于 NMR 和 HR-MS，设计、合成并表征了 Leucetta 生物碱 kealiinines A-C 和 kealiinine B 衍生物。首次评价了这些生物碱的抗 TMV 和抗植物病原真菌活性。与 kealiinines A 和 C 相比，kealiinine B 表现出更高的抗 TMV 活性。kealiinine B 衍生物 2m（在 500 μg/mL 时的体内失活、治疗和保护活性的抑制率分别为 68%、66%和 71%）和 2y（在 500 μg/mL 时的体内失活、治疗和保护活性的抑制率分别为 69%、64%和 63%）表现出明显更高的抗病毒活性，优于宁南霉素（在 500 μg/mL 时的体内失活、治疗和保护活性的抑制率分别为 56%、56%和 58%），因此成为新型抗病毒药物开发的新先导化合物。构效关系研究为这些生物碱的结构简化提供了依据。进一步的杀菌活性测试表明，这些生物碱对核盘菌和禾谷丝核菌表现出广谱的杀菌活性。化合物 2i 和 2p 表现出良好的体外杀菌活性，对核盘菌和禾谷丝核菌的抑制率分别为 71%/50mg/kg 和 70%/50mg/kg。
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