Anti-proliferative lichen compounds with inhibitory activity on 12(S)-HETE production in human platelets.
Several lichen compounds, i.e. lobaric acid (1), a beta-orcinol depsidone from Stereocaulon alpinum L., (+)-protolichesterinic acid (2), an aliphatic alpha-methylene-gamma-lactone from Cetraria islandica Laur. (Parmeliaceae), (+)-usnic acid (3), a dibenzofuran from Cladonia arbuscula (Wallr.) Rabenh. (Cladoniaceae), parietin (4), an anthraquinone from Xanthoria elegans (Link) Th. Fr. (Calaplacaceae) and baeomycesic acid (5), a beta-orcinol depside isolated from Thamnolia vermicularis (Sw.) Schaer. var. subuliformis (Ehrh.) Schaer. were tested for inhibitory activity on platelet-type 12(S)-lipoxygenase using a cell-based in vitro system in human platelets. Lobaric acid (1) and (+)-protolichesterinic acid (2) proved to be pronounced inhibitors of platelet-type 12(S)-lipoxygenase, whereas baeomycesic acid (5) showed only weak activity (inhibitory activity at a concentration of 100 microg/ml: (1) 93.4+/-6.62%, (2) 98,5+/-1.19%, 5 14.7+/-2.76%). Usnic acid (3) and parietin (4) were not active at this concentration. 1 and 2 showed a clear dose-response relationship in the range of 3.33-100 microg/ml. According to the calculated IC50 values the highest inhibitory activity was observed for the depsidone 1 (IC50 = 28.5 microM) followed by 2 (IC50 = 77.0 microM). The activity of 1 was comparable to that of the flavone baicalein, which is known as a selective 12(S)-lipoxygenase inhibitor (IC50 = 24.6 microM).
Bucar
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Institute of Pharmacognosy, University of Graz, Universitaetsplatz 411, A-8010 Graz, Austria.
Schneider
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Ogmundsdóttir
H
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Ingólfsdóttir
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K
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / Q000096:biosynthesis*; D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D001565:Benzoates / Q000494:pharmacology; D001572:Benzofurans / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology; D053630:Depsides; D004642:Emodin / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007783:Lactones / Q000494:pharmacology; D008011:Lichens / Q000737:chemistry*; D008084:Lipoxygenase / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors; D015394:Molecular Structure; D012118:Resorcinols / Q000494:pharmacology; D012459:Salicylates / Q000494:pharmacology
D001565:Benzoates; D001572:Benzofurans; D053630:Depsides; D007783:Lactones; D016859:Lipoxygenase Inhibitors; D012118:Resorcinols; D012459:Salicylates; C496299:baeomycesic acid; C073339:usnic acid; C095781:protolichesterinic acid; C104417:lobaric acid; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D008084:Lipoxygenase; C008905:physcione; D004642:Emodin; D015107:4-Butyrolactone