Functionalized Glycomers as Growth Inhibitors and Inducers of Apoptosis in Human Glioblastoma Cells

• Published in: Journal of medicinal chemistry 2003-08, Vol.46 (17), p.3600-3611
• Main Authors: Hanessian, Stephen, Zhan, Lijie, Bovey, Raymonde, Saavedra, Oscar M, Juillerat-Jeanneret, Lucienne
• Format: Article
• Language: English
• Subjects: Antineoplastic agents; Apoptosis; Biological and medical sciences; Brain Neoplasms - pathology; Cell Division - drug effects; Cell Line; Cerebral Cortex - cytology; Endothelium - cytology; Endothelium - drug effects; Fibroblasts - cytology; Fibroblasts - drug effects; General aspects; Glioblastoma - pathology; Glucosides - chemical synthesis; Glucosides - chemistry; Glucosides - pharmacology; Humans; Medical sciences; Pharmacology. Drug treatments; Tumor Cells, Cultured
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm0205853

The effects of functionalized aryl β-d-glycopyranosides (glycomers) on the proliferation, survival, and apoptosis of human glioblastoma cells in culture were evaluated as a way to control tumor progression. The results showed that inhibition of growth and/or induction of apoptosis can be achieved by these molecules in human glioblastoma cells. Inhibition of DNA synthesis precedes induction of apoptosis and growth inhibition. The substituents at C-1, C-2, C-3,C-4, and C-6 on the pyranosidic scaffold are important to modulate the action and the efficacy of these molecules. Human fibroblasts and brain-derived endothelial cells were less sensitive to glycomers than tumor cells. Thus, functionalized aryl β-d-glycopyranosides represent a new class of molecules potentially able to control the progression of brain tumors.