New Immunomodulating Glycosyl Ceramides from Marine Sponges

The scientific interest on the immunological properties of glycosphingolipids (GSLs) is recently increased on account of the role that they could play as therapeutic agents. An interesting aspect of these properties is the immunomodulating activity reported for a number of GSLs. Agelasphins, galactosylceramides isolated from marine sponge Agelas mauritianus, exhibited immunostimulating activity, which was suggested to be related to the interesting in vivo antitumoral properties ofthese compounds through an activation of the immune system. In our continuing studies on glycolipids from marine sponges we have examined the extracts of four species of the genus Agelas and we have isolated a whole new class of GSLs, characterized by an α-galactosyl as the sugar directly linked to the ceramide. All the GSLs isolated were tested for immunostimulating activity, using the mixed lymphocyte reaction (MLR) assay. The obtained results suggest that the immunostimulating activity is affected by a specific structural feature of the GSLs, namely glycosylation of the inner sugar at position 2. Infact, all the immunostimulating compounds possess a free 2-OH on the sugar directly linked to the ceramide moìety, while this activity disappears if this position is glycosylated either by an α-galactosyl or by an α-glucosyl.