title: Discovery of (2-benzoylethen-1-ol)-containing 1,2-benzothiazine derivatives as novel 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibiting-based herbicide lead compounds.
abstract: A series of (2-benzoylethen-1-ol)-containing benzothiazine derivatives was synthesized, and their herbicidal activities were first evaluated. The bioassay results indicated that some of 3-benzoyl-4-hydroxy-2-methyl-2H-1,2-benzothiazine-1,1-dioxide derivatives displayed good herbicidal activity in greenhouse testing, especially, compound 4w had good pre-emergent herbicidal activities against Brassica campestris, Amaranthus retroflexus and Echinochloa crusgalli even at a dosage of 187.5 g ha(-1). More importantly, compound 4w displayed significant inhibitory activity against Arabidopsis thaliana HPPD and was identified as the most potent candidate with IC50 value of 0.48 μM, which is better than the commercial herbicide sulctrione (IC50=0.53 μM) and comparable with the commercial herbicide mesotrione (IC50=0.25 μM). The structure-activity relationships was studied and provided some useful information for improving herbicidal activity. The present work indicated that (2-benzoylethen-1-ol)-containing 1,2-benzothiazine motif could be a potential lead structure for further development of novel HPPD inhibiting-based herbicides.
authors.affiliation: State Key Laboratory of Elemento-Organic Chemistry, Institute of Elemento-Organic Chemistry, Nankai University, Tianjin, China; Collaborative Innovation Center of Chemical Science and Engineering, Tianjin, China.
authors.forename: Kang
authors.initials: K
authors.lastname: Lei
authors.affiliation: State Key Laboratory of Elemento-Organic Chemistry, Institute of Elemento-Organic Chemistry, Nankai University, Tianjin, China; Collaborative Innovation Center of Chemical Science and Engineering, Tianjin, China.
authors.forename: Xue-Wen
authors.initials: XW
authors.lastname: Hua
authors.affiliation: State Key Laboratory of Elemento-Organic Chemistry, Institute of Elemento-Organic Chemistry, Nankai University, Tianjin, China; Collaborative Innovation Center of Chemical Science and Engineering, Tianjin, China.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Tao
authors.affiliation: State Key Laboratory of Elemento-Organic Chemistry, Institute of Elemento-Organic Chemistry, Nankai University, Tianjin, China; Collaborative Innovation Center of Chemical Science and Engineering, Tianjin, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Elemento-Organic Chemistry, Institute of Elemento-Organic Chemistry, Nankai University, Tianjin, China; Collaborative Innovation Center of Chemical Science and Engineering, Tianjin, China.
authors.forename: Na
authors.initials: N
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Elemento-Organic Chemistry, Institute of Elemento-Organic Chemistry, Nankai University, Tianjin, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Elemento-Organic Chemistry, Institute of Elemento-Organic Chemistry, Nankai University, Tianjin, China.
authors.forename: Yong-Hong
authors.initials: YH
authors.lastname: Li
authors.affiliation: State Key Laboratory of Elemento-Organic Chemistry, Institute of Elemento-Organic Chemistry, Nankai University, Tianjin, China; Collaborative Innovation Center of Chemical Science and Engineering, Tianjin, China. Electronic address: xiaohuaxu@nankai.edu.cn.
authors.forename: Xiao-Hua
authors.initials: XH
authors.lastname: Xu
authors.affiliation: College of Resources and Environmental Sciences, China Agricultural University, Beijing, China.
authors.forename: Chui-Hua
authors.initials: CH
authors.lastname: Kong
mesh_terms: D015111:4-Hydroxyphenylpyruvate Dioxygenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D027721:Amaranthus / Q000187:drug effects; D017360:Arabidopsis / Q000187:drug effects / Q000201:enzymology*; D001937:Brassica / Q000187:drug effects; D003499:Cyclic S-Oxides / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D031747:Echinochloa / Q000187:drug effects; D006540:Herbicides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013843:Thiazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C000606503:1,2-benzothiazine; D003499:Cyclic S-Oxides; D006540:Herbicides; D013843:Thiazines; D015111:4-Hydroxyphenylpyruvate Dioxygenase
keywords: 4-Hydroxyphenylpyruvate dioxygenase; Benzothiazine; Herbicide activity; Structure–activity relationships; Synthesis