New pyridinium alkaloids from a marine sponge of the genus Spongia with a 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 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 microM, with an IC(50) value of 5.8 microM 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.
De Marino
S
S
Dipartimento di Chimica delle Sostanze Naturali, Università degli Studi di Napoli "Federico II", via D. Montesano 49, 80131 Napoli, Italy.
Iorizzi
M
M
Zollo
F
F
Debitus
C
C
Menou
J L
JL
Ospina
L F
LF
Alcaraz
M J
MJ
Payá
M
M
D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D000818:Animals; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D006801:Humans; D015394:Molecular Structure; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D011161:Porifera / Q000737:chemistry*; D011726:Pyridinium Compounds / Q000737:chemistry; D013057:Spectrum Analysis
D000470:Alkaloids; D004791:Enzyme Inhibitors; D011726:Pyridinium Compounds; D010741:Phospholipases A