Indolizines as novel potent inhibitors of 15-lipoxygenase

Bioorg Med Chem. 2003 Dec 1;11(24):5409-15. doi: 10.1016/j.bmc.2003.09.033.

Abstract

15-Lipoxygenase (15-LO) has been implicated in oxidation of low-density lipoproteins (LDL) and this enzyme may be involved in the development of atherosclerosis. We have examined 1-substituted indolizines as possible inhibitors of 15-LO from soy beans and from rabbit reticulocytes. Most compounds studied were significantly more active as inhibitors of 15-LO from soy beans than quercetin. The indolizines were slightly less potent inhibitors of the mammalian enzyme, but we found good correlation between inhibitory activity against both 15-LO enzymes studied. Several of the compounds were only weak DPPH scavengers and they may therefore be regarded as so-called non antioxidant inhibitors of 15-LO.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arachidonate 15-Lipoxygenase / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Glycine max / enzymology
  • Indolizines / pharmacology*
  • Lipoproteins, LDL / metabolism
  • Lipoxygenase Inhibitors*
  • Quercetin / pharmacology
  • Rabbits
  • Reticulocytes / enzymology

Substances

  • Enzyme Inhibitors
  • Indolizines
  • Lipoproteins, LDL
  • Lipoxygenase Inhibitors
  • Quercetin
  • Arachidonate 15-Lipoxygenase