Design of novel tryptamine-based SDHI fungicides inspired by rice phytoalexins: Antifungal activity evaluation and molecular mechanism

Globally, biotic stress—predominantly caused by plant-pathogenic fungi—results in substantial annual crop losses and significant economic costs, thereby posing a continuing threat to agricultural sustainability. Addressing the dual challenges of limited effective agrochemical availability and rapidly evolving pathogen resistance requires the urgent development of novel green fungicides. Inspired by phytoalexins, we designed a series of new pyrazole-carboxylic acid derivatives incorporating a tryptamine motif as potential succinate dehydrogenase inhibitor (SDHI). Most of the compounds exhibited inhibitory activity against eight common phytopathogenic fungi. Among them, compounds 8 and 23 showed significant activity against Sclerotinia sclerotiorum , with EC₅₀ values of 15.7 μmol/L and 19.8 μmol/L, respectively. Activity tests in vivo revealed that compounds 8 and 23 protected oilseed rape leaves and tomato fruits from infection by Sclerotinia sclerotiorum and Botrytis cinerea at a concentration of 100 μmol/L. The inhibition effects of compounds 8 and 23 against succinate dehydrogenase were 6.13 and 6.16 μmol/L, respectively, better than Thirluzamide (IC₅₀ = 9.38 μmol/L). Scanning electron microscopy analysis, molecular docking, and DFT calculation confirmed that the mode of action of these compounds was similar to Fluopyram. Molecular design inspired by phytoalexins offers a new avenue for further developing succinate dehydrogenase inhibitors.