Portal de Periódicos da CAPES

Petrosaspongiolides M−R: New Potent and Selective Phospholipase A 2 Inhibitors from the New Caledonian Marine Sponge Petrosaspongia n igra

1998; American Chemical Society; Volume: 61; Issue: 5 Linguagem: Inglês

10.1021/np9704922

1520-6025

Antonio Randazzo, Cécile Debitus, Luigi Minale, P. García Pastor, María José Alcaraz, M. Payá, Luigi Gomez‐Paloma,

Cholinesterase and Neurodegenerative Diseases

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 A2 (PLA2) 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 PLA2 enzymes. The most potent compound, 1 (IC50 1.6 and 0.6 μM for human synovial and bee venom PLA2 enzymes, respectively), was slightly more active than manoalide (6) (IC50 3.9 and 7.5 μM) under our experimental conditions. Compound 3 is more selective, inhibiting human synovial PLA2 to a greater extent than bee venom PLA2.