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

Abstract

O-acetyl-ganglioside neurostatin, (Galbeta1-->3GalNAcbeta1-->4[9-O-Ac Neu5Acalpha2-->8Neu5Acalpha2-->3]Galbeta1-->4Glcbeta1-->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 set-up 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.

• Authors: Beatriz Valle-Argos, Diego Gómez-Nicola, Manuel Nieto-Sampedro
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 45 Issue 5 Pg. 2034-43 (May 2010) ISSN: 1768-3254 [Electronic] France
• PMID: 20153569 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright (c) 2010 Elsevier Masson SAS. All rights reserved.

Chemical References

• Antineoplastic Agents
• Glycosphingolipids
• neurostatin

Topics

• Animals
• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Drug Screening Assays, Antitumor
• Glioma (drug therapy, pathology)
• Glycosphingolipids (chemical synthesis, chemistry, pharmacology)
• Humans
• Rats
• Structure-Activity Relationship