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

• Published in: Journal of natural products (Washington, D.C.) Vol. 63; no. 3; pp. 322 - 326
• Main Authors: De Marino, S, Iorizzi, M, Zollo, F, Debitus, C, Menou, JL, Ospina, LF, Alcaraz, MJ, Paya, M
• Format: Journal Article
• Language: English
• Published: WASHINGTON Amer Chemical Soc 01.03.2000
• Subjects: Alkaloids - chemistry; Alkaloids - isolation & purification; Alkaloids - pharmacology; Animals; Chemistry, Medicinal; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - isolation & purification; Enzyme Inhibitors - pharmacology; Humans; Life Sciences & Biomedicine; Molecular Structure; Pharmacology & Pharmacy; Phospholipases A - antagonists & inhibitors; Plant Sciences; Porifera - chemistry; Pyridinium Compounds - chemistry; Science & Technology; Spectrum Analysis; POTENT; PETROSASPONGIA-NIGRA; MANOALIDE; LUFFARIELLA SP
• ISSN: 0163-3864
• DOI: 10.1021/np990374+

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 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 alkaloids (5-8) mainly inhibited human synovial PLA(2). Compound 8, which contains a sulfonic acid group, is the most interesting inhibitor.