New bis-catechols 5-lipoxygenase inhibitors

Bioorg Med Chem. 2001 Feb;9(2):229-35. doi: 10.1016/s0968-0896(00)00258-3.

Abstract

Three polyhydroxy-2-phenylnaphthalenes (1-3) and the oxy analogue of tetrahydroxypavinan (4) were prepared and evaluated for their antioxidant properties (inhibition of diphenylpycrylhydrazyl radical (DPPH), reduction of iron (III) ion) and inhibition of 5-lipoxygenase (5-LO) activity. Their three-dimensional structures were established on the basis of spectroscopic data and semiempirical calculations. Compounds 1 and 2 were found as potent 5-LO inhibitors as nordihydroguaiaretic acid (NDGA), whereas 4 is 2.5 times less potent than NDGA. The reliability of the 3-D structures with the 5-LO inhibition properties is discussed. Their antioxidant properties show that tested compounds are expected to act as redox inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / chemical synthesis
  • Antioxidants / pharmacology
  • Arachidonate 5-Lipoxygenase / drug effects*
  • Arachidonate 5-Lipoxygenase / metabolism
  • Bepridil / analogs & derivatives*
  • Bepridil / metabolism
  • Biphenyl Compounds
  • Catechols
  • Indicators and Reagents
  • Iron / metabolism
  • Kinetics
  • Lipoxygenase Inhibitors / chemical synthesis*
  • Lipoxygenase Inhibitors / pharmacology
  • Molecular Structure
  • Oxidation-Reduction
  • Picrates*
  • Rats
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Antioxidants
  • Biphenyl Compounds
  • Catechols
  • Indicators and Reagents
  • Lipoxygenase Inhibitors
  • Picrates
  • Bepridil
  • 1,1-diphenyl-2-picrylhydrazyl
  • Iron
  • Arachidonate 5-Lipoxygenase