Design, synthesis and antifungal activity of arylhydrazine analogs containing diphenyl ether fragments

Background: Succinate dehydrogenase (SDH) represents a critical target in the development of novel fungicides. To address the growing issue of resistance and safeguard the economic viability of agricultural production, the pursuit of new succinate dehydrogenase inhibitors (SDHIs) has emerged as a significant focus of contemporary research.

Results: In this project, 32 arylhydrazine derivatives containing diphenyl ether structural units were synthesized and evaluated for their fungicidal activities against Rhizoctonia solani, Sclerotinia sclerotiorum, Alternaria alternata, Gibberella zeae, Alternaria solani and Colletotrichum gloeosporioides. In an in vitro fungicidal activity assay, compound D6 showed significant inhibitory activity against R. solani with a half-maximum effective concentration (EC₅₀) of 0.09 mg L^-1. The in vivo fungicidal activity demonstrated that compound D6 inhibited R. solani by 95.39% in rice leaves, which was significantly better than that of boscalid (85.76%). The results of SDH enzyme assay, molecular docking simulation, mitochondrial membrane potential assay, cytoplasmic release studies and morphological observations demonstrated that the target compound D6 not only had significant SDH inhibitory activity, but also affected the membrane integrity of mycelium.

Conclusion: Bioactivity screening and validation of the mechanism of action indicated that compound D6 was a potentially unique SDHI, acting on SDH while also affecting cell membrane permeability, which deserved further study. © 2024 Society of Chemical Industry.