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Marine Natural Products for Drug Discovery: First Discovery of Kealiinines A–C and Their Derivatives as Novel Antiviral and Antiphytopathogenic Fungus Agents

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journal contribution
posted on 05.07.2018 by Gang Li, Jincheng Guo, Ziwen Wang, Yuxiu Liu, Haibin Song, Qingmin Wang
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.

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