title: Synthesis and Herbicidal Activity of Triketone-Quinoline Hybrids as Novel 4-Hydroxyphenylpyruvate Dioxygenase Inhibitors.
abstract: 4-Hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27, HPPD) is one of the most important targets for herbicide discovery. In the search for new HPPD inhibitors with novel scaffolds, triketone-quinoline hybrids were designed and subsequently optimized on the basis of the structure-activity relationship (SAR) studies. Most of the synthesized compounds displayed potent inhibition of Arabidopsis thaliana HPPD (AtHPPD), and some of them exhibited broad-spectrum and promising herbicidal activity at the rate of 150 g ai/ha by postemergence application. Most promisingly, compound III-l, 3-hydroxy-2-(2-methoxy-7-(methylthio)quinoline-3-carbonyl)cyclohex-2-enone (Ki = 0.009 μM, AtHPPD), had broader spectrum of weed control than mesotrione. Furthermore, compound III-l was much safer to maize at the rate of 150 g ai/ha than mesotrione, demonstrating its great potential as herbicide for weed control in maize fields. Therefore, triketone-quinoline hybrids may serve as new lead structures for novel herbicide discovery.
authors.forename: Da-Wei
authors.initials: DW
authors.lastname: Wang
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Lin
authors.forename: Run-Jie
authors.initials: RJ
authors.lastname: Cao
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
authors.forename: Feng-Xu
authors.initials: FX
authors.lastname: Wu
authors.forename: Ge-Fei
authors.initials: GF
authors.lastname: Hao
authors.forename: Qiong
authors.initials: Q
authors.lastname: Chen
authors.forename: Wen-Chao
authors.initials: WC
authors.lastname: Yang
authors.affiliation: ‡Collaborative Innovation Center of Chemical Science and Engineering, Tianjin 30071, People's Republic of China.
authors.forename: Guang-Fu
authors.initials: GF
authors.lastname: Yang
mesh_terms: D015111:4-Hydroxyphenylpyruvate Dioxygenase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D017360:Arabidopsis / Q000201:enzymology; D029681:Arabidopsis Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006540:Herbicides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D007659:Ketones / Q000737:chemistry*; D057685:Plant Weeds / Q000187:drug effects / Q000254:growth & development; D011804:Quinolines / Q000737:chemistry*; D013329:Structure-Activity Relationship; D058728:Weed Control
chemical_list: D029681:Arabidopsis Proteins; D004791:Enzyme Inhibitors; D006540:Herbicides; D007659:Ketones; D011804:Quinolines; C037219:quinoline; D015111:4-Hydroxyphenylpyruvate Dioxygenase
keywords: 4-hydroxyphenylpyruvate dioxygenase; herbicide; quinoline; rational design; triketone