fuscol and Edema

The octocoral-derived terpenes fuscol and eunicol are known, potent anti-inflammatory agents. While total syntheses of one of the parent natural products have been published, the economic and practical feasibility of producing commercially viable amounts of material is very low. Based on the observation that the characteristic dienol of fuscol, eunicol and related compounds is conserved in anti-inflammatory activity, this project aimed to remove the structural complexity of the substituted cyclohexane and cyclodecadiene of fuscol and eunicol, respectively. The synthesis of a small panel of structurally simpler fuscol/eunicol analogues was completed and five of the six new compounds were found to have slightly superior activity to the parent natural products.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Biological Products; Diterpenes; Dose-Response Relationship, Drug; Ear; Edema; Mice; Molecular Structure; Structure-Activity Relationship; Tetradecanoylphorbol Acetate

A new dilophol diterpene, eunicidiol (1), has been isolated from the crude extract of Eunicea fusca, a gorgonian coral collected from Hillsboro Ledge, Florida. This compound was purified, along with fuscol (2) and eunicol (3), using a combination of normal- and reversed-phase chromatography methods. The structure of eunicidiol (1) was elucidated by 1D and 2D NMR spectroscopic analysis, and the absolute configuration was assigned using Mosher's method. The anti-inflammatory activity of 1-3 was evaluated by measuring their ability to reduce phorbol myristate acetate (PMA)-induced edema in a mouse ear model. Topical application of a 100 μg/ear dose of diterpenes 1-3 significantly reduced edema by 44%, 46%, and 54%, respectively. This activity was superior to indomethacin, a known anti-inflammatory used as a control.

Topics: Animals; Anthozoa; Anti-Inflammatory Agents, Non-Steroidal; Diterpenes; Edema; Indomethacin; Mice; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Tetradecanoylphorbol Acetate

The screen of 10 soft coral extracts collected from the Colombian Caribbean Sea in the TPA-induced ear edema model allowed us to identify Eunicea fusca extract among others as an interesting source of active compounds. The new diterpene, fuscoside E (1), along with the known fuscoside B (2), fuscol (3), (+)-germacrene D (4) and a mixture of six sterols (5-10), were isolated from this soft coral. Their structures were elucidated by 1D and 2D NMR spectroscopy techniques. Fuscoside E (1) absolute stereochemistry was determined by chiroptical methods. Fuscoside E (1) and B (2) showed strong anti-inflammatory in the above mentioned bioassay. Additionally, fuscoside E (1) and the sterol mixture (5-10) presented antifouling activity against bacterial strains involved in surface colonization.

Topics: Animals; Anthozoa; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Bacillus; Biological Assay; Biological Products; Caribbean Region; Disease Models, Animal; Diterpenes; Drug Discovery; Drug Evaluation, Preclinical; Ear; Edema; Glycosides; Mice; Microbial Sensitivity Tests; Molecular Conformation; Molecular Structure; Stereoisomerism; Vibrio