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The marine metabolite bolinaquinone is a novel inhibitor of secretory phospholipase A(2) (sPLA(2)), with a potency on the human synovial enzyme (group II) higher than that of manoalide. This activity on the sPLA(2) was confirmed in vivo in the 8-h zymosan rat air pouch on the secretory enzyme accumulation in the pouch exudate. Additionally, bolinaquinone decreased potently the synthesis and release of leukotriene B(4) (LTB(4)) in calcimycin (A23187)-stimulated human neutrophils as a consequence of the inhibition of 5-lipoxygenase activity, as well as PGE(2) and NO production on zymosan-stimulated mouse peritoneal macrophages. This compound exerted anti-inflammatory effects by topical and oral routes on the mouse ear edema induced by 12-O-tetradecanoylphorbolacetate, with ID(50) values of 76.7 microg/ear and 5.6 mg/kg, respectively, with a significant decrease in PGE(2), LTB(4), and tumor necrosis factor-alpha (TNF-alpha) levels being more effective than indomethacin. This effect was confirmed in the mouse paw carrageenan edema after oral administration. Moreover, bolinaquinone was able to reduce the inflammatory response of adjuvant arthritis by inhibiting PGE(2), NO, and TNF-alpha production in paw homogenates without affecting PGE(2) levels in the stomach. Additionally, bolinaquinone inhibited inducible nitric oxide synthase expression and reduced the degree of bone resorption, soft tissue swelling, and osteophyte formation.

A new nonsymmetric dimeric steroid, crellastatin A (1), was isolated from the Vanuatu Island marine sponge Crella sp. Structural assignment was accomplished through extensive 2D NMR spectroscopy. The stereochemistry of 1 was established from an analysis of ROESY experiments and from molecular mechanics and dynamics calculations. Crellastatin A (1), which possesses an unprecedented connection through the side chains, exhibits in vitro cytotoxic activity against NSCLC-N6 cells (IC(50) of 1.5 &mgr;g/mL).