Petrosaspongiolides M-R: new potent and selective phospholipase A2 inhibitors from the New Caledonian marine sponge Petrosaspongia nigra

• Published in: Journal of natural products (Washington, D.C.) Vol. 61; no. 5; pp. 571 - 575
• Main Authors: Randazzo, A, Debitus, C, Minale, L, Pastor, P.G, Alcaraz, M.J, Paya, M, Gomez-Paloma, L
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 01-05-1998; Glendale, AZ American Society of Pharmacognosy
• Subjects: 4-Butyrolactone - analogs & derivatives; 4-Butyrolactone - chemistry; 4-Butyrolactone - isolation & purification; 4-Butyrolactone - pharmacology; ANIMAL DISEASES; Animals; ANTIVENOMS; APIDAE; BEE VENOM; Bee Venoms - enzymology; Biological and medical sciences; CERDO; CHEMICAL COMPOSITION; CHEMICAL STRUCTURE; COMPOSICION QUIMICA; COMPOSITION CHIMIQUE; CULEBRA; DESINTOXICANTES; DETOXICANT; DETOXICANTS; DIGESTIVE SYSTEM DISEASES; ENFERMEDADES DE LOS ANIMALES; ENFERMEDADES DEL SISTEMA DIGESTIVO; ENZYME INHIBITORS; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - isolation & purification; Enzyme Inhibitors - pharmacology; EPONGE; ESPECTROMETRIA; ESPONJAS; ESTERASAS; ESTERASE; ESTERASES; ESTRUCTURA QUIMICA; General pharmacology; GENERO HUMANO; GENRE HUMAIN; HUMAN SINOVIAL; Humans; INHIBIDORES DE ENZIMAS; INHIBITEUR D'ENZYME; Magnetic Resonance Spectroscopy; MALADIE DE L'APPAREIL DIGESTIF; MALADIE DES ANIMAUX; MANKIND; Medical sciences; MEDICINAL PROPERTIES; Molecular Structure; NAJA NAJA; NEW CALEDONIA; NOUVELLE CALEDONIE; NUEVA CALEDONIA; PANCREAS; Pancreas - enzymology; PARAZOA; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Phospholipases A - antagonists & inhibitors; Phospholipases A2; PORCIN; Porifera - chemistry; PROPIEDADES MEDICINALES; PROPRIETE PHARMACOLOGIQUE; SERPENT; SESTERTERPENES; SNAKES; SPECTRAL ANALYSIS; SPECTROMETRIE; SPECTROMETRY; Spectrometry, Mass, Fast Atom Bombardment; SPONGES; STRUCTURE CHIMIQUE; SWINE; Synovial Fluid - enzymology; Terpenes - chemistry; Terpenes - isolation & purification; Terpenes - pharmacology; TERPENOIDE; TERPENOIDOS; TERPENOIDS; VENENOS; VENIN; VENOMS; New Caledonia; Melanesia; Oceania; Insecta; Alcohol; Esterases; Oxygen heterocycle; Marine environment; Acylal; Acylate; Ungulata; Human; Terpenoid; Enzyme; Enzyme inhibitor; Animal origin; Lactone; Tetracyclic compound; In vitro; Phospholipase A; Biological activity; Carboxylic ester hydrolases; Ophidia; Pig; Vertebrata; Mammalia; Porifera; Arthropoda; Animal; Hydrolases; Isolation; Reptilia; Artiodactyla; Invertebrata; Hymenoptera; Naja naja; Sesterterpenes; Structural analysis
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/np9704922

Five new bioactive sesterterpenes (1-5) have been isolated from the New Caledonian marine sponge Petrosaspongia nigra Bergquist and named petrosaspongiolides M-R. Their chemical structures were determined from 1D and 2D NMR studies and MS data. All compounds inhibited different preparations of phospholipase A2 (PLA2) by irreversibly blocking these enzymes (particularly human synovial and bee venom, see Table 3), with IC50 values in the micromolar range. Interestingly, these compounds displayed a much lower activity (or no activity at all) toward porcine pancreas and Naja naja venom PLA2 enzymes. The most potent compound, 1 (IC50 1.6 and 0.6 microM for human synovial and bee venom PLA2 enzymes, respectively), was slightly more active than manoalide (6) (IC50 3.9 and 7.5 microM) under our experimental conditions. Compound 3 is more selective, inhibiting human synovial PLA2 to a greater extent than bee venom PLA2.