Petrosaspongiolides M-R: New Potent and Selective Phospholipase A2 Inhibitors from the New Caledonian Marine Sponge Petrosaspongia nigra

Five new bioactive sesterterpenes (1-5) have been isolated from the New Caledonian marine sponge Petrosaspongia nigra Bergquist and named petrosaspongiolides M-R. Their chemical structures were determined from 1D and 2D NMR studies and MS data. All compounds inhibited different preparations of phospholipase A(2) (PLA(2)) by irreversibly blocking these enzymes (particularly human synovial and bee venom, see Table 3), with IC50 values in the micromolar range. Interestingly, these compounds displayed a much lower activity (or no activity at all) toward porcine pancreas and Naja naja venom PLA(2) enzymes. The most potent compound, 1 (IC50 1.6 and 0.6 mu M for human synovial and bee venom PLA(2) enzymes, respectively), was slightly more active than manoalide (6) (IC50 3.9 and 7.5 mu M) under our experimental conditions. Compound 3 is more selective, inhibiting-human synovial PLA(2) to a greater extent than bee venom PLA(2).