Cavernolide:: a new inhibitor of human sPLA2 sharing unusual chemical features

The inhibitory effect of cavernolide, a novel C-21 terpene lactone isolated from the sponge Fascio-spongia cavernosa, on PLA(2) and other enzyme activities involved in the inflammatory process was studied. Cavernolide inhibited human synovial sPLA(2) in a concentration-dependent manner with an IC50 value of 8.8 muM. Besides, this compound decreased in the nanomolar range the myeloperoxidase degranulation process using different stimuli. Cavernolide also inhibited TNF alpha, NO and PGE(2) production in intact cell experiments. NO and PGE(2) reduction was the consequence of the inhibition on iNOS and COX-2 expression because it did not affect inducible nitric oxide synthase and cyclooxygenase-2 activities in intact cells. (C) 2000 Elsevier Science Inc. All rights reserved.