Novel succinate dehydrogenase inhibitors containing oxime ester structures: design, synthesis, and biological activities

Abstract

The development of succinate dehydrogenase inhibitors (SDHIs) is crucial for ensuring sustainable food production. This study introduces a novel class of aryl oxime ester derivatives to improve antifungal activity. In vitro experiments showed that compounds with methylene linkers showed better biological activity. Compound A7 exhibited potent inhibition against Fusarium graminearum (EC₅₀ = 1.07 µg mL⁻¹), outperforming fluxapyroxad (FLU; EC₅₀ = 5.15 µg mL⁻¹). In vivo trials demonstrated 67.14% suppression at 100 µg mL⁻¹, indicating potential field application. Enzymatic inhibition studies confirmed the inhibition of A7 (IC₅₀ = 34.33 µM), approaching that of FLU (IC₅₀ = 15.95 µM). Docking studies indicated that the A7 carbonyl can form hydrogen bonds similar to those formed by FLU, while the π–π interaction of A7 plays a key role in SDH binding. This structural synergy underscores the role of oxime esters in optimizing SDHI binding affinity. This work establishes aryl oxime esters as an effective skeleton for SDHI optimization, providing a promising scaffold for future development.