1'-Hydroxyeugenol- and coniferyl alcohol derivatives as effective inhibitors of 5-lipoxygenase and Cu(2+)-mediated low density lipoprotein oxidation. Evidence for a dual mechanism.
1'-Hydroxyeugenol- and epoxy-Z-coniferyl alcohol esters from Coreopsis species as well as synthetic derivatives of these natural compounds were examined as lipoxygenase inhibitors and as LDL (low density lipoprotein)-stabilizing agents. Most of the compounds displayed inhibitory activity on the formation of leukotrienes (LTB4 and LTC4) in a cellular (RBL-1 cells) assay as well as in a cell-free 5-lipoxygenase assay at concentrations of 4-24 mumol/l. No effect of selected compounds was observed on mammalian lipoxygenases with other specificity (12- and 15-lipoxygenase). The more lipophilic derivatives also effectively reduced Cu(2+)-mediated oxidation of LDL. The findings are discussed on the base of structure-activity relationships.
Deigner
H P
HP
Pharmazeutisch-Chemisches Institut, Universität Heidelberg, Fed. Rep. of Germany.
Wolf
G
G
Ohlenmacher
U
U
Reichling
J
J
D000818:Animals; D001092:Arachidonate 12-Lipoxygenase / Q000378:metabolism; D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D003300:Copper / Q000502:physiology*; D005054:Eugenol / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D015471:Leukemia, Basophilic, Acute / Q000378:metabolism; D007975:Leukotriene B4 / Q000378:metabolism; D017997:Leukotriene C4 / Q000378:metabolism; D008074:Lipoproteins / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D010084:Oxidation-Reduction; D010636:Phenols / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D008074:Lipoproteins; D016859:Lipoxygenase Inhibitors; D010636:Phenols; D007975:Leukotriene B4; D017997:Leukotriene C4; D005054:Eugenol; D003300:Copper; C010559:coniferyl alcohol; D001092:Arachidonate 12-Lipoxygenase; D001093:Arachidonate 15-Lipoxygenase; D001094:Arachidonate 5-Lipoxygenase