New pyridinium alkaloids from a marine sponge of the genus Spongia with human phospholipase A(2) inhibitor profile

Four new bioactive pyridinium alkaloids, named spongidines A-D (5-8), have been isolated from a Vanuatu sponge of the genus Spongia, together with kno wn petrosaspongiolides D (1) and G (2). Compounds 3 and 4 are 21-hydroxy de rivatives of petrosaspongiolides K and P. Structure elucidation was accompl ished through extensive 2D NMR experiments (COSY, ROESY, HMBC, HMQC) and IR , UV, and FABMS data. All compounds significantly inhibited human synovial phospholipase A(2) (PLA(2)) at 10 mu M, with, an IC50 value of 5.8 mu M for compound 4, which is the most potent inhibitor, with a higher selectivity toward this enzyme than the reference inhibitor manoalide, Pyridinium alkal oids (5-8) mainly inhibited human synovial PLA(2). Compound 8, which contai ns a sulfonic acid group, is the most interesting inhibitor.