NOVEL MONOSACCHARIDES AS POTENT INHIBITORS OF CELL-PROLIFERATION

The effects of several novel monosaccharides upon thymidine incorporat ion into both normal and tumour cells were investigated. The monosacch aride 2-deoxy-3-[1 -(R)-(ethoxycarbonyl)ethyl]-alpha-D-allo-pyranose h ad the most inhibitory effect on proliferation, with the (S)-enantiome r having less inhibitory effects. The chiral centre at carbon-7 was fo und to be an important part of the molecule. as 2-deoxy-3-[methoxycarb onyl methyl]-alpha-D-allo-pyranose had greatly decreased anti-prolifer ative properties in comparison with the parent compound. In addition, the 2-deoxy structure at carbon-2 was also found to be important, as ) -(ethoxycarbonyl)ethyl]-alpha-D-allo-hexopyranose had greatly decrease d inhibitory properties in comparison with the parent compound. The re sults indicate that these novel monosaccharides possess potent anti-pr oliferative properties, related to their chiral carbon-7 and 2-deoxy c arbon-2 structure and suggest that further substitutions of the functi onal group at carbon-7 may improve these properties and possibly produ ce inhibitor selectivity for tumour cells in preference to normal cell s. (C) 1997 John Wiley & Sons, Ltd.