Natural products in crop protection: thiosemicarbazone derivatives of 3-acetyl-N-benzylindoles as antifungal agents and their mechanism of action

Background 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. Results Derivatives displayed potent antifungal activity against V. mali . Notably, 3-acetyl- N -benzylindole thiosemicarbazone (IV-1: EC 50 : 0.59 μ g mL −1 ), whose activity was comparable to that of a commercial fungicide carbendazim (EC 50 : 0.33 μ g mL −1 ), 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. Conclusion 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.