Marine polyprenylated hydroquinones, quinones, and chromenols with inhibitory effects on leukotriene formation

A series of polyprenylated hydroquinones, quinones, and chromenols were isolated from the extracts of the marine sponge Ircinia spinosula and the brown alga Taonia atomaria, which gave rise to the constituents 1-4 and 5-8, respectively. Compounds 1, 2, 6, and 7 are new natural products, which were fully characterized. Their anti-inflammatory activities in terms of leukotriene formation were evaluated in an in vitro assay with pork leukocytes. The new hydroxylated compound, 2'-[28-hydroxy]heptaprenyl-1',4'-hydroquinone (= 2-[(2E,6E,10E,14E,18Z,22E)-19-(hydroxymethyl)-3,7,11,15,23,27-hexamethyloctacosa-2,6,10,14,18,22,26-heptaen-1-yl]benzene-1,4-diol; 1), the known tetraprenyl benzoquinone sargaquinone (5), and the known polyprenyl chromenols 3 and 4 exhibited the highest anti-inflammatory activities, with IC50 values of 1.9-9.4 microM (Table 3). Potential structure-activity relationships (SAR) are discussed.