Polyoxygenated Dysidea sterols that inhibit the binding of [I125] IL-8 to the human recombinant IL-8 receptor type A

The combined CH2Cl2 and MeOH crude extract of a new species of the marine sponge Dysidea, collected in Northern Australia was found to inhibit the binding of [I125] interleukin-8 [IL-8] to the human recombinant IL-8 receptor type A at 500 mu g/mL. Bioassay-guided fractionation led to the isolation of three new polyoxygenated sterols 3, 4, and 5. Their structures were assigned on the basis of 1D and 2D NMR, experiments, and relative stereochemistries were established by ROESY correlations and analysis of coupling constants. The IC50 values for inhibition of IL-8Ra for sterols 3, 4, and 5 were 20, 5.5, and 4.5 mu M, respectively.