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

Chem Biol Drug Des. 2014 Oct;84(4):431-42. doi: 10.1111/cbdd.12331. Epub 2014 May 12.

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.

Keywords: benzothiazole hexahydro-1H-isoindole-1,3(2H)-dione; herbicidal activity; hexahydro-1H-isoindol-1-one; protoporphyrinogen oxidase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Crystallography, X-Ray
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / toxicity
  • Herbicides / chemical synthesis*
  • Herbicides / chemistry
  • Herbicides / toxicity
  • Isoindoles / chemical synthesis
  • Isoindoles / chemistry*
  • Isoindoles / toxicity
  • Molecular Conformation
  • Molecular Docking Simulation
  • Nicotiana / metabolism
  • Plant Roots / drug effects
  • Plant Roots / growth & development
  • Plant Shoots / drug effects
  • Plant Shoots / growth & development
  • Protein Structure, Tertiary
  • Protoporphyrinogen Oxidase / antagonists & inhibitors*
  • Protoporphyrinogen Oxidase / genetics
  • Protoporphyrinogen Oxidase / metabolism
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics

Substances

  • Enzyme Inhibitors
  • Herbicides
  • Isoindoles
  • Recombinant Proteins
  • Protoporphyrinogen Oxidase