3D‐QSAR model‐oriented optimization of Pyrazole β‐Ketonitrile derivatives with diphenyl ether moiety as novel potent succinate dehydrogenase inhibitors
IF 3.8
1区 农林科学
Q1 AGRONOMY
Liangliang Cheng, Cong Zhou, Qinglong Yuan, Letian Zhang, Xusheng Shao, Xiaoyong Xu, Zhong Li, Jiagao Cheng
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Abstract
BACKGROUNDSuccinate 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.RESULTSAiming 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 (EC50 ) value of 0.0398 μg mL−1 comparable to that for fluxapyroxad (EC50 = 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 μm . 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.CONCLUSIONThe 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.
以 3D-QSAR 模型为导向,优化具有二苯醚分子的吡唑 β-Ketonitrile 衍生物,使其成为新型强效琥珀酸脱氢酶抑制剂
背景琥珀酸脱氢酶抑制剂(SDHI)杀菌剂在植物真菌病害防治中发挥着重要作用。然而,它们正面临着抗药性和交叉抗性问题的严峻挑战,这主要归因于它们的频繁应用和结构相似性。结果为了发现新型强效的 SDHI 杀菌剂,我们以之前研究的 3D-QSAR 模型为指导,合理设计并合成了 31 个具有二苯醚分子的创新型吡唑 β-酮腈衍生物。最佳目标化合物 A23 不仅在体外对根瘤菌具有出色的抑制活性,其半最大有效浓度(EC50)值为 0.0398 μg mL-1,与氟吡甲禾灵(EC50 = 0.0375 μg mL-1)相当,而且在体内对水稻鞘枯病具有中等程度的保护效力。猪琥珀酸脱氢酶(SDH)酶抑制试验表明,A23 是一种强效的 SDH 抑制剂,其半最大抑制浓度为 0.0425 μm。在 R. solani SDH 中的 Docking 研究表明,A23 主要通过氢键、阳离子-π 和 π-π 相互作用有效地结合到泛醌位点。© 2024 化学工业协会。
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来源期刊
期刊介绍:
Pest Management Science is the international journal of research and development in crop protection and pest control. Since its launch in 1970, the journal has become the premier forum for papers on the discovery, application, and impact on the environment of products and strategies designed for pest management.
Published for SCI by John Wiley & Sons Ltd.