1-HYDROXYETHYLHALENAQUINONE: A NEW PROTEASOME INHIBITOR FROM THE MARINE SPONGE XESTOSPONGIA SP.

A new halenaquinone derivative, 1-hydroxyethylhalenaquinone (1), was isolated from the marine sponge Xestospongia sp. as a proteasome inhibitor together with three known compounds, halenaquinone (2) and 3-ketoadociaquinones A (3) and B (4). 1-Hydroxyethylhalenaquinone (1) was the first halenaquinone derivative containing an alkyl group at the keto-furan C-1 position. Compounds 1 and 2 inhibited the chymotrypsin-like activity of the proteasome with IC50 values of 0.19 and 0.63 mu M, respectively, whereas 3 or 4, each containing a thiomorpholine 1,1-dioxide moiety, scarcely inhibited its activity, even at a concentration of 5 mu M.