部分
杀菌剂
化学
琥珀酸脱氢酶
吡唑
体内
IC50型
体外
乙醚
立体化学
生物化学
酶
组合化学
有机化学
生物
生物技术
植物
作者
Liangliang Cheng,Cong Zhou,Qinglong Yuan,Letian Zhang,Xusheng Shao,Xiaoyong Xu,Zhong Li,Jiagao Cheng
摘要
Abstract BACKGROUND Succinate dehydrogenase inhibitor (SDHI) fungicides play important roles in the control of plant fungal diseases. However, they are facing serious challenges from issues with resistance and cross‐resistance, primarily attributed to their frequent application and structural similarities. There is an urgent need to design and develop SDHI fungicides with novel structures. RESULTS Aiming to discover novel potent SDHI fungicides, 31 innovative pyrazole β ‐ketonitrile derivatives with diphenyl ether moiety were rationally designed and synthesized, which were guided by a 3D‐QSAR model from our previous study. The optimal target compound A23 exhibited not only outstanding in vitro inhibitory activities against Rhizoctonia solani with a half‐maximal effective concentration (EC 50 ) value of 0.0398 μg mL −1 comparable to that for fluxapyroxad (EC 50 = 0.0375 μg mL −1 ), but also a moderate protective efficacy in vivo against rice sheath blight. Porcine succinate dehydrogenase (SDH) enzymatic inhibitory assay revealed that A23 is a potent inhibitor of SDH, with a half‐maximal inhibitory concentration of 0.0425 μ m . Docking study within R. solani SDH indicated that A23 effectively binds into the ubiquinone site mainly through hydrogen‐bonds, and cation–π and π–π interactions. CONCLUSION The identified β ‐ketonitrile compound A23 containing diphenyl ether moiety is a potent SDH inhibitor, which might be a good lead for novel fungicide research and optimization. © 2024 Society of Chemical Industry.
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