NOVEL DISACCHARIDE INHIBITORS OF HUMAN GLIOMA CELL-DIVISION

Several alpha-L-Fuc-(1-->3)-alpha-D-GlcNAcOC(8)H(17) disaccharide deri vatives bearing different hydroxylated alkyl chains, with or without s ulfate groups at C-4 and/or C-6 positions of the GlcNAc unit, have bee n synthesized and-tested as inhibitors of human astrocytoma Lines U-37 3 and U-118. The antimitotic activity was dependent on the structure a nd position of the hydroxylated chain linked to the disaccharide. The compounds with a pentaerythritol or L-glyceryl chain at the C-6 positi on showed the best inhibitory properties, with an ID50 value of ca. 20 0 mu M. On the contrary, sulfated disaccharide derivatives were inacti ve. The antimitotic activities of the compounds tested were essentiall y independent of the mitogen used to stimulate cell division.