A New Cacospongionolide Inhibitor of Human Secretory Phospholipase A2 from the Tyrrhenian Sponge Fasciospongia cavernosa and Absolute Configuration of Cacospongionolides

• Published in: Journal of natural products (Washington, D.C.) D.C.), 1998-07, Vol.61 (7), p.931-935
• Main Authors: De Rosa, Salvatore, Crispino, Antonio, De Giulio, Alfonso, Iodice, Carmine, Benrezzouk, Rachid, Terencio, M. Carmen, Ferrándiz, M. Luisa, Alcaraz, M. José, Payá, Miguel
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cyprinodontiformes; Drug Screening Assays, Antitumor; Enzyme Inhibitors - isolation & purification; Enzyme Inhibitors - pharmacology; Enzyme Inhibitors - toxicity; Furans - isolation & purification; Furans - pharmacology; Furans - toxicity; General pharmacology; Humans; Magnetic Resonance Spectroscopy; Mass Spectrometry; Medical sciences; Molecular Conformation; Pancreas - enzymology; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Phospholipases A - antagonists & inhibitors; Phospholipases A2; Porifera - chemistry; Pyrans - isolation & purification; Pyrans - pharmacology; Pyrans - toxicity; Spectrophotometry, Infrared; Spectrophotometry, Ultraviolet; Synovial Fluid - enzymology; Venoms - enzymology
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/np980122t

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.