Inhibiting human astrocytoma growth: structure-activity relationships in neurostatin related glycolipids.

Abstract

Neurostatin, a mammalian brain inhibitor of division of astroblast and astrocytoma cells, was characterized as the disialoganglioside GD1b, 9-O-acetylated on the outer sialic acid residue (Galbeta1-->3GalNAcbeta1-->4(9-O-Ac-NeuAcalpha2-->8NeuAcalpha2-->3)Galbeta1-->4Glcbeta1-->1'-ceramide). Using semisynthetic approaches, we prepared and tested different gangliosides O-acetylated in the sialic acid and compared them to non-O-acetylated partners as inhibitors of U-373 glioma cells. Athough the O-acetylation of the sialic acid was the most important molecular feature for the antiproliferative activity of O-acetylated gangliosides, monosaccharide links Galbeta1--> 3GalNAcbeta1 and NeuAcalpha2-->8NeuAcalpha2 enhanced the inhibitory activity.

• Authors: Lorenzo Romero-Ramírez, Manuel Nieto-Sampedro
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 47 Issue 21 Pg. 4983-4 (Oct 07 2004) ISSN: 0022-2623 [Print] United States
• PMID: 15456241 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Gangliosides
• Glycolipids
• Glycosphingolipids
• neurostatin
• N-Acetylneuraminic Acid

Topics

• Acetylation
• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Astrocytoma (pathology)
• Brain Neoplasms (pathology)
• Cell Division (drug effects)
• Cell Line, Tumor
• Gangliosides (chemical synthesis, chemistry, pharmacology)
• Glycolipids (chemical synthesis, chemistry, pharmacology)
• Glycosphingolipids (chemistry)
• Humans
• N-Acetylneuraminic Acid (chemistry)
• Structure-Activity Relationship