Synthesis and characterization of neurostatin-related compounds with high inhibitory activity of glioma growth

O-acetyl-ganglioside neurostatin, (Galf beta 1 -> 3GalNAc beta 1 -> 4[9-O-Ac Neu5Ac alpha 2 -> 8Neu5Ac alpha 2 -> 3]Gal beta 1 -> 4Glc beta 1 -> 1'-ceramide), is a natural GD1b-derived inhibitor of astroblast and astrocytoma division, whose structure and purification method limits its availability and stability. Therefore, we setup the reaction to obtain O-acetylated and O-butyrylated neurostatin analogs by chemical synthesis, in order to improve its availability and stability. The compounds antitumoral activity was evaluated on U373MG and C6 glioblastoma cells, observing that the O-acetylation-dependent increase in the inhibitory activity was enhanced by O-butyrylation, with no further improvement with the multi-substitution, pointing to the initial conformational change and the stability change as responsible of its function. These results open the possibility for the application of the neurostatin-related compounds to in-vivo tumoral models. (C) 2010 Elsevier Masson SAS. All rights reserved.