Lucas Rut, Casapullo Agostino, Ciasullo Linda, Gomez-Paloma Luigi, Payá Miguel
Departamento de Farmacología. Universidad de Valencia. Facultad de Farmacia. Av. Vicent Andrés Estellés s/n, 46100, Valencia, Burjasot, Spain.
Life Sci. 2003 Apr 18;72(22):2543-52. doi: 10.1016/s0024-3205(03)00167-x.
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.
