New Pyridinium Alkaloids from a Marine Sponge of the Genus Spongia with a Human Phospholipase A2 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 known petrosaspongiolides D (1) and G (2). Compounds 3 and 4 are 21-hydroxy derivatives of petrosaspongiolides K and P. Structure elucidation was accomplished 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 μM, with an IC 50 value of 5.8 μM for compound 4, which is the most potent inhibitor, with a higher selectivity toward this enzyme than the reference inhibitor manoalide. Pyridinium alkaloids (5-8) mainly inhibited human synovial PLA 2 . Compound 8, which contains a sulfonic acid group, is the most interesting inhibitor.