Abstract BACKGROUND The misuse, abuse and long‐term application of fungicides have led to a continuous increase in the resistance of plant pathogenic fungi. Therefore, the development of fungicides with novel structure, broad‐spectrum inhibition and high efficiency has become an urgent challenge. RESULTS This study designed and synthesized 40 novel oxime ester amide derivatives and investigated their antifungal activity, most of the target compounds had the best inhibitory effect on Sclerotinia sclerotiorum . Among the target compounds, compounds 7c and 7d exhibited the best in vitro inhibitory activity against S. sclerotiorum , the median effective concentration (EC 50 ) of compounds 7c (0.264 μg/mL) and 7d (0.436 μg/mL) were significantly lower than fluxapyroxad (EC 50 = 0.557 μg/mL). It is noteworthy that the median inhibitory concentration (IC 50 ) values of compounds 7c and 7d against succinate dehydrogenase (SDH) were 0.535 and 0.798 μg/mL, respectively, which were also substantially lower than fluxapyroxad (IC 50 = 0.891 μg/mL). And the inhibitory activities of compounds 7c and 7d against SDH were also further verified through fluorescence quenching. Finally, molecular docking was employed to simulate the interaction mechanisms of compounds 7c and fluxapyroxad, with binding energies of compounds 7c (−10.4 kcal/mol), 7d (−8.2 kcal/mol) and positive control (−7.9 kcal/mol), respectively. CONCLUSION These results clearly confirmed that compounds 7c and 7d as structurally novel succinate dehydrogenase inhibitors (SDHIs) not only exhibit outstanding antifungal activity but also demonstrate potential value in overcoming critical issues such as drug resistance, presenting broad prospects for research and development. © 2026 Society of Chemical Industry.
Liu et al. (Wed,) studied this question.