Anti-proliferative lichen compounds with inhibitory activity on 12(S)-HETE production in human platelets

Abstract Several lichen compounds, i.e. lobaric acid ( 1 ), a β-orcinol depsidone from Stereocaulon alpinum L., (+)-protolichesterinic acid ( 2 ), an aliphatic α-methylene-γ-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 β-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 μg/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 μg/ml. According to the calculated IC 50 values the highest inhibitory activity was observed for the depsidone 1 (IC 50 =28.5 μM) followed by 2 (IC 50 =77.0 μM). The activity of 1 was comparable to that of the flavone baicalein, which is known as a selective 12( S )-lipoxygenase inhibitor (IC 50 =24.6 μM).