Oreacerebrosides, new bioactive cerebrosides with a triunsaturated sphingoid base from the sea star

The sea star Oreaster reticulatus contains, along with the known ophidiacerebrosides C-E, nine new glycosphingolip- ids named oreacerebrosides A-I. Their structures were eluci- dated by a combination of spectroscopic methods and chemi- cal degradation. All compounds contain a 4,8,10-triunsatur- ated sphingoid base. Oreacerebrosides A-C have a ?-gluco- pyranoside as the sugar residue, as found in ophidiacerebros- ides C-E and in all known compounds of this type; in con- trast, oreacerebrosides D-I are the first examples of ?-galac- tosylceramides containing this unusual sphingoid base. Four epresentative glycosphingolipids were tested for cytotoxic activity on rat glioma C6 cells and were shown to be mildly cytotoxic; the glucosylceramides were more active than the galactosylceramides. In addition, oreacerebroside I, but not ophidiacerebroside E, was shown to exert proangiogenic ac- tivity and was able to increase VEGF-induced human endo- thelial cell proliferation.