title: Synthesis, in vitro protoporphyrinogen oxidase inhibition, and herbicidal activity of N-(benzothiazol-5-yl)hexahydro-1H-isoindole-1,3-diones and N-(benzothiazol-5-yl)hexahydro-1H-isoindol-1-ones.
abstract: Protoporphyrinogen oxidase (EC 1.3.3.4) is one of the most significant targets for a large family of herbicides. As part of our continuous efforts to search for novel protoporphyrinogen oxidase-inhibiting herbicides, N-(benzothiazol-5-yl)tetrahydroisoindole-1,3-dione was selected as a lead compound for structural optimization, leading to the syntheses of a series of novel N-(benzothiazol-5-yl)hexahydro-1H-isoindole-1,3-diones (1a-o) and N-(benzothiazol-5-yl)hexahydro-1H-isoindol-1-ones (2a-i). These newly prepared compounds were characterized by elemental analyses, (1) H NMR, and ESI-MS, and the structures of 1h and 2h were further confirmed by X-ray diffraction analyses. The bioassays indicated that some compounds displayed comparable or higher protoporphyrinogen oxidase inhibition activities in comparison with the commercial control. Very promising, compound 2a, ethyl 2-((6-fluoro-5-(4,5,6,7-tetrahydro-1-oxo-1H-isoindol-2(3H)-yl)benzo[d]thiazol-2-yl)-sulfanyl)acetate, was recognized as the most potent candidate with K(i) value of 0.0091 μm. Further greenhouse screening results demonstrated that some compounds exhibited good herbicidal activity against Chenopodium album at the dosage of 150 g/ha.
authors.affiliation: Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, Wuhan, 430079, China.
authors.forename: Qiong-You
authors.initials: QY
authors.lastname: Wu
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Jiang
authors.forename: Yang
authors.initials: Y
authors.lastname: Zuo
authors.forename: Zhi-Fang
authors.initials: ZF
authors.lastname: Wang
authors.forename: Zhen
authors.initials: Z
authors.lastname: Xi
authors.forename: Guang-Fu
authors.initials: GF
authors.lastname: Yang
mesh_terms: D001665:Binding Sites; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D006540:Herbicides / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D054833:Isoindoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D018517:Plant Roots / Q000187:drug effects / Q000254:growth & development; D018520:Plant Shoots / Q000187:drug effects / Q000254:growth & development; D017434:Protein Structure, Tertiary; D050768:Protoporphyrinogen Oxidase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D014026:Nicotiana / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D006540:Herbicides; D054833:Isoindoles; D011994:Recombinant Proteins; D050768:Protoporphyrinogen Oxidase
keywords: benzothiazole hexahydro-1H-isoindole-1,3(2H)-dione; herbicidal activity; hexahydro-1H-isoindol-1-one; protoporphyrinogen oxidase