Novel monosaccharides as potent inhibitors of cell proliferation.
The effects of several novel monosaccharides upon thymidine incorporation into both normal and tumour cells were investigated. The monosaccharide 2-deoxy-3-[1-(R)-(ethoxycarbonyl)ethyl]- alpha-D-allo-pyranose had the most inhibitory effect on proliferation, with the (S)-enantiomer having less inhibitory effects. The chiral centre at carbon-7 was found to be an important part of the molecule, as 2-deoxy-3-[methoxycarbonyl methyl]-alpha-D-allo-pyranose had greatly decreased anti-proliferative properties in comparison with the parent compound. In addition, the 2-deoxy structure at carbon-2 was also found to be important, as 3-[1-(S)-(ethoxycarbonyl)ethyl]-alpha-D-allo-hexopyranose had greatly decreased inhibitory properties in comparison with the parent compound. The results indicate that these novel monosaccharides possess potent anti-proliferative properties, related to their chiral carbon-7 and 2-deoxy carbon-2 structure and suggest that further substitutions of the functional group at carbon-7 may improve these properties and possibly produce inhibitor selectivity for tumour cells in preference to normal cells.
Colquhoun
A
A
Department of Biochemistry, University of Oxford, U.K.
Alaluf
S
S
Bradley
A
A
Gemmell
N
N
Gibbs
G
G
Osborn
H M
HM
Harwood
L M
LM
Newsholme
E A
EA
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001011:Aorta / Q000166:cytology; D001943:Breast Neoplasms; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms; D004247:DNA / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007822:Laryngeal Neoplasms; D007938:Leukemia; D051379:Mice; D009005:Monosaccharides / Q000138:chemical synthesis* / Q000494:pharmacology*; D051381:Rats; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001749:Urinary Bladder Neoplasms
D000970:Antineoplastic Agents; D009005:Monosaccharides; D004247:DNA; D005947:Glucose