Novel Disaccharide Inhibitors of Human Glioma Cell Division

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Abstract
Several α-l-Fuc-(1→3)-α-d-GlcNAcOC8H17 disaccharide derivatives bearing different hydroxylated alkyl chains, with or without sulfate groups at C-4 and/or C-6 positions of the GlcNAc unit, have been synthesized and tested as inhibitors of human astrocytoma lines U-373 and U-118. The antimitotic activity was dependent on the structure and position of the hydroxylated chain linked to the disaccharide. The compounds with a pentaerythritol or l-glyceryl chain at the C-6 position showed the best inhibitory properties, with an ID50 value of ca. 200 μM. On the contrary, sulfated disaccharide derivatives were inactive. The antimitotic activities of the compounds tested were essentially independent of the mitogen used to stimulate cell division.