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.
Tziveleka
Leto-A
LA
School of Pharmacy, Department of Pharmacognosy and Chemistry of Natural Products, University of Athens, Panepistimiopolis Zografou, Athens, Greece.
Abatis
Dennis
D
Paulus
Kerstin
K
Bauer
Rudolf
R
Vagias
Constantinos
C
Roussis
Vassilios
V
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology; D001578:Benzopyrans / Q000737:chemistry* / Q000494:pharmacology; D006873:Hydroquinones / Q000737:chemistry* / Q000494:pharmacology; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D015289:Leukotrienes / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors; D015394:Molecular Structure; D011161:Porifera / Q000737:chemistry*; D011809:Quinones / Q000737:chemistry* / Q000494:pharmacology; D013552:Swine
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001578:Benzopyrans; D006873:Hydroquinones; D015289:Leukotrienes; D016859:Lipoxygenase Inhibitors; D011809:Quinones