Probing sponge-derived terpenoids for human 15-lipoxygenase inhibitors

A human 15-lipoxygenase (15-HLO) assay has been employed to discover new marine-sponge-derived bioactive compounds. Extracts from two different sponges, Jaspis splendens (order Choristida, family Jaspidae) and Suberea sp. (order Verongida, family Aplysinellidae), exhibited potent IC50 values of 0.4 and 0.1 mug/mL, respectively. Both are sources of terpenoids, and the former is a known source of (+)-jasplakinolide (7), which is inactive as a 15-HLO inhibitor. The terpenoids included (+)-(5S,6S)-subersin (1, IC50 > 100 muM), (-)-(5R,10R)-subersic acid (2, IC50 = 15 muM), jaspaquinol (3, IC50 = 0.3 muM), and (-)-jaspic acid (4, IC50 = 1.4 muM). Structure elucidations and lipoxygenase activity studies of these compounds are reported.