title: Cycloamphilectenes, a new type of potent marine diterpenes: inhibition of nitric oxide production in murine macrophages.
abstract: The inhibitory effect of a series of 6 cycloamphilectenes, novel marine diterpenes based on amphilectene skeletons and isolated from the Vanuatu sponge Axinella sp., on NO, PGE(2) and TNFalpha production in murine peritoneal macrophages was studied. These compounds reduced potently nitric oxide production in a concentration-dependent manner with IC(50) values in the submicromolar range (0.1-4.3 microM). Studies on intact cells and Western blot analysis showed that the more potent cycloamphilectenes reduced the expression of inducible nitric oxide synthase without affecting cyclo-oxygenase-2 expression. Among them cycloamphilectene 2, the unique compound bearing an exocyclic methylene group, was able to reduce NO production without affecting TNFalpha release. Cycloamphilectene 2, which is an inhibitor of the nuclear factor-kB pathway, exhibited topical anti-inflammatory activity.
authors.affiliation: Departamento de Farmacología. Universidad de Valencia. Facultad de Farmacia. Av. Vicent Andrés Estellés s/n, 46100, Valencia, Burjasot, Spain.
authors.forename: Rut
authors.initials: R
authors.lastname: Lucas
authors.forename: Agostino
authors.initials: A
authors.lastname: Casapullo
authors.forename: Linda
authors.initials: L
authors.lastname: Ciasullo
authors.forename: Luigi
authors.initials: L
authors.lastname: Gomez-Paloma
authors.forename: Miguel
authors.initials: M
authors.lastname: Payá
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D015153:Blotting, Western; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000096:biosynthesis; D004224:Diterpenes / Q000737:chemistry / Q000494:pharmacology*; D004487:Edema / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000096:biosynthesis; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D008387:Marine Toxins / Q000737:chemistry / Q000494:pharmacology*; D008565:Membrane Proteins; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D010196:Pancreatic Elastase / Q000378:metabolism; D011161:Porifera / Q000737:chemistry*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004224:Diterpenes; D007527:Isoenzymes; D008387:Marine Toxins; D008565:Membrane Proteins; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D010196:Pancreatic Elastase; D015232:Dinoprostone