Indolizines as novel potent inhibitors of 15-lipoxygenase.
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.
Gundersen
Lise-Lotte
LL
Department of Chemistry, University of Oslo, PO Box 1033, Blindern, N-0315 Oslo, Norway. l.l.gundersen@kjemi.uio.no
Malterud
Karl E
KE
Negussie
Ayele H
AH
Rise
Frode
F
Teklu
Solomon
S
Østby
Ole Benny
OB
D000818:Animals; D001093:Arachidonate 15-Lipoxygenase / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007212:Indolizines / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000378:metabolism; D016859:Lipoxygenase Inhibitors; D011794:Quercetin / Q000494:pharmacology; D011817:Rabbits; D012156:Reticulocytes / Q000201:enzymology; D013025:Glycine max / Q000201:enzymology
D004791:Enzyme Inhibitors; D007212:Indolizines; D008077:Lipoproteins, LDL; D016859:Lipoxygenase Inhibitors; D011794:Quercetin; D001093:Arachidonate 15-Lipoxygenase