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RESEARCH PRODUCT
Cycloamphilectenes, a new type of potent marine diterpenes: inhibition of nitric oxide production in murine macrophages.
Linda CiasulloRut LucasMiguel PayáLuigi Gomez-palomaAgostino Casapullosubject
NeutrophilsBlotting WesternNitric Oxide Synthase Type IIElectrophoretic Mobility Shift AssayIn Vitro TechniquesNitric OxideGeneral Biochemistry Genetics and Molecular BiologyDinoprostoneNitric oxidechemistry.chemical_compoundMiceStructure-Activity RelationshipWestern blotmedicineAnimalsEdemaHumansGeneral Pharmacology Toxicology and PharmaceuticsMethylenebiologymedicine.diagnostic_testPancreatic ElastaseTumor Necrosis Factor-alphaMacrophagesZymosanAnti-Inflammatory Agents Non-SteroidalAxinellaNF-kappa BMembrane ProteinsGeneral Medicinebiology.organism_classificationPoriferaNitric oxide synthaseIsoenzymesSpongechemistryBiochemistryCyclooxygenase 2Prostaglandin-Endoperoxide Synthasesbiology.proteinMacrophages PeritonealTumor necrosis factor alphaFemaleMarine ToxinsDiterpenesNitric Oxide Synthasedescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2003-04-01 | Life sciences |