College of Plant Protection, Northwest A&F University, Yangling, China.
Key Laboratory of Vector Biology and Pathogen Control of Zhejiang Province, College of Life Science, Huzhou University, Huzhou, China.
Pest Manag Sci. 2023 Aug;79(8):2801-2810. doi: 10.1002/ps.7457. Epub 2023 Mar 31.
Phytopathogenic fungi can cause a direct loss in economic value of agriculture. Especially Valsa mali Miyabe et Yamada, a devastating phytopathogenic disease especially threatening global apple production, is very difficult to control and manage. To discover new potential antifungal agents, a series of thiosemicarbazone derivatives of 3-acetyl-N-benzylindoles were prepared. Their antifungal activities were first tested against six typically phytopathogenic fungi including Curvularia lunata, Valsa mali, Alternaria alternate, Fusarium graminearum, Botrytis cinerea and Fusarium solani. Then their mechanism of action against V. mali was investigated.
Derivatives displayed potent antifungal activity against V. mali. Notably, 3-acetyl-N-benzylindole thiosemicarbazone (IV-1: EC : 0.59 μg mL ), whose activity was comparable to that of a commercial fungicide carbendazim (EC : 0.33 μg mL ), showed greater than 98-fold antifungal activity of the precursor indole. Moreover, compound IV-1 displayed good protective and therapeutic effects on apple Valsa canker disease. By scanning electron microscope (SEM) and RNA-Seq analysis, it was demonstrated that compound IV-1 can destroy the hyphal structure and regulate the homeostasis of metabolism of V. mali via the ergosterol biosynthesis and autophagy pathways.
3-Acetyl-N-(un)substituted benzylindoles thiosemicarbazones (IV-1-IV-5) can be studied as leads for further structural modification as antifungal agents against V. mali. Particularly, these ergosterol biosynthesis and autophagy pathways can be used as target receptors for design of novel green pesticides for management of congeneric phytopathogenic fungi. © 2023 Society of Chemical Industry.
植物病原真菌可导致农业的直接经济价值损失。特别是梨轮纹病菌（Valsa mali Miyabe et Yamada），一种严重威胁全球苹果生产的植物病原病害，极难防治。为发现新的潜在抗真菌剂，我们制备了一系列 3-乙酰基-N-苯并吲哚缩硫脲衍生物。首次测试了它们对包括新月弯孢菌（Curvularia lunata）、梨轮纹病菌、交链孢菌（Alternaria alternate）、禾谷镰刀菌（Fusarium graminearum）、灰葡萄孢（Botrytis cinerea）和茄腐镰刀菌（Fusarium solani）在内的六种典型植物病原真菌的抗真菌活性。然后研究了它们对梨轮纹病菌的作用机制。
衍生物对梨轮纹病菌表现出很强的抗真菌活性。值得注意的是，3-乙酰基-N-苯并吲哚缩硫脲（IV-1：EC：0.59μg/mL）的活性与商业杀真菌剂多菌灵（EC：0.33μg/mL）相当，对前体吲哚的抗真菌活性大于 98 倍。此外，化合物 IV-1 对苹果腐烂病具有良好的保护和治疗作用。通过扫描电子显微镜（SEM）和 RNA-Seq 分析，证明化合物 IV-1 可以通过破坏菌丝结构和调节麦角甾醇生物合成和自噬途径来调节梨轮纹病菌的代谢平衡。
3-乙酰基-N-（未）取代苯并吲哚缩硫脲（IV-1-IV-5）可作为进一步结构修饰的先导化合物，作为抗梨轮纹病菌的抗真菌剂。特别是这些麦角甾醇生物合成和自噬途径可作为设计新型绿色农药防治同类植物病原真菌的靶标受体。© 2023 化学工业协会。
