Discovery of 4-Hydroxyphenylpyruvate dioxygenase inhibitors with novel pharmacophores  

作　　者：Tai-Li Yang Jin Dong Xin-Long Wang Jiangqing Dong Hong-Yan Lin 

机构地区：[1]State Key Laboratory of Green Pesticide,Central China Normal University,Wuhan,430079,PR China [2]International Joint Research Center for Intelligent Biosensor Technology and Health,Central China Normal University,Wuhan,430079,PR China [3]Hubei Shizhen Laboratory,Wuhan,430061,PR China [4]School of Basic Medical Sciences,Hubei University of Chinese Medicine,Wuhan,430065,PR China

出　　处：《Advanced Agrochem》2024年第4期344-350,共7页现代农业化学（英文）

基　　金：National Key Research and Development Program of China(No.2023YFD1700500);National Natural Science Foundation of China(22377031);Hubei Provincial Science and Technology Plan Project(2022BEC051);Knowledge Innovation Program of Wuhan-Basic Research(No.2022013301015174);Key Research and Development Program of Hubei Province(2022BBA001).

摘　　要：4-Hydroxyphenylpyruvate dioxygenase(HPPD)is pivotal in tyrosine metabolism and essential for plant survival.Its inhibition leads to leaf bleaching and plant death.While current HPPD inhibitors are effective,they pose phytotoxicity risks and may contribute to herbicide resistance.Here,we investigated the inhibitory potential of sethoxydim and atovaquone,which traditionally target acetyl-CoA carboxylase and the cytochrome bc1 complex,respectively.Both atovaquone and the degradation product of sethoxydim exhibited moderate HPPD inhibitory activity.But the mechanism by which sethoxydim inhibited HPPD remained unclear.Therefore,we embarked on an investigation into the crystal structure of the complex,with the aim of elucidating its precise binding mode.Our findings revealed that sethoxydim degrades in solution,producing dealkoxy sethoxydim as the active component in HPPD inhibition.Structural analysis elucidated the binding modes of atovaquone and dealkoxy sethoxydim with HPPD.These binding motifs represent novel pharmacophores and offer promising leads for developing HPPD inhibitors with improved pesticidal profiles.

关 键 词：METABOLISM PRECISE traditionally 

分 类 号：TQ4[化学工程]