A new cacospongionolide inhibitor of human secretory phospholipase A2 from the Tyrrhenian sponge Fasciospongia cavernosa and absolute configuration of cacospongionolides.
A new inhibitor of human secretory phospholipase A2 (PLA2), cacospongionolide E (4a), has been isolated from the Tyrrhenian sponge Fasciospongia cavernosa. The structure was proposed on the basis of spectroscopic data and by chemical transformations. The absolute configuration of cacospongionolides 2a-4a was established using the modified Mosher's method. Cacospongionolide E was the most potent inhibitor toward human synovial PLA2, showing higher potency than the reference compound manoalide and exerting no signs of toxicity on human neutrophils. It showed high activity in the Artemia salina bioassay and moderate toxicity in the fish (Gambusia affinis) lethality assay.
De Rosa
S
S
Istituto per la Chimica di Molecole di Interesse Biologico CNR, via Toiano 6, 80072 Arco Felice (Napoli), Italy. sdr@sdr.icmib.na.cnr.it
Crispino
A
A
De Giulio
A
A
Iodice
C
C
Benrezzouk
R
R
Terencio
M C
MC
Ferrándiz
M L
ML
Alcaraz
M J
MJ
Payá
M
M
D000818:Animals; D003532:Cyprinodontiformes; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000302:isolation & purification* / Q000494:pharmacology / Q000633:toxicity; D005663:Furans / Q000302:isolation & purification* / Q000494:pharmacology / Q000633:toxicity; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008968:Molecular Conformation; D010179:Pancreas / Q000201:enzymology; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2; D011161:Porifera / Q000737:chemistry*; D011714:Pyrans / Q000302:isolation & purification* / Q000494:pharmacology / Q000633:toxicity; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet; D013582:Synovial Fluid / Q000201:enzymology; D014688:Venoms / Q000201:enzymology
D004791:Enzyme Inhibitors; D005663:Furans; D011714:Pyrans; D014688:Venoms; D010741:Phospholipases A; D054467:Phospholipases A2