A NEW CACOSPONGIONOLIDE INHIBITOR OF HUMAN SECRETORY PHOSPHOLIPASE A(2) FROM THE TYRRHENIAN SPONGE FASCIOSPONGIA-CAVERNOSA AND ABSOLUTE-CONFIGURATION OF CACOSPONGIONOLIDES

A new inhibitor of human secretory phospholipase A(2) (PLA(2)), cacosp ongionolide E (4a), has been isolated from the Tyrrhenian sponge Fasci ospongia cavernosa. The structure was proposed on the basis of spectro scopic data and by chemical transformations. The absolute configuratio n of cacospongionolides 2a-4a was established using the modified Moshe r's method. Cacospongionolide E was the most potent inhibitor toward h uman synovial PLA(2), showing higher potency than the reference compou nd manoalide and exerting no signs of toxicity on human neutrophils. I t showed high activity in the Artemia salina bioassay and moderate tox icity in the fish (Gambusia affinis) lethality assay.