CARB 36 |
| We have demonstrated significant activity of 2-deoxy-D-glucose (2-DG) and its analogs in chemotherapeutically resistant tumors of the brain and pancreas. Inhibition of tumor cell growth can occur under hypoxia or normoxia by interfering directly with monosaccharide metabolism. 2-Halo-substituted derivatives of D-glucose and D-mannose were synthesized and a comparison of their biological properties indicated with increase size of the substituted halogen (i.e. F > Cl > Br) D-glucose derivatives became less effective in inhibiting growth under aerobic vs. hypoxic conditions. Moreover, 2-deoxy-2-fluoro-D-glucose shows better activity than 2-DG in our assays. Additionally, the change in orientation of the fluorine atom from D-gluco to D-manno configuration does not significantly alter the growth inhibitory activity. Overall, our results suggest that monosaccharide-based antimetabolites such as 2-DG and 2-FG will be useful clinically in selectively targeting glycolytic tumor cells. |
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Sugar Alley Symposium
8:30 AM-12:10 PM, Tuesday, April 8, 2008 Morial Convention Center -- Rm. 223, Oral
Division of Carbohydrate Chemistry |