Indolizines as novel potent inhibitors of 15-lipoxygenase
Lise-Lotte Gundersen1, Karl E Malterud, Ayele H Negussie
1Department of Chemistry, University of Oslo, PO Box 1033, Blindern, N-0315 Oslo, Norway. l.l.gundersen@kjemi.uio.no
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.
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