Hexose keto-C-glycoside conjugates: design, synthesis, cytotoxicity, and evaluation of their affinity for the glucose transporter Glut-1.
The design, synthesis, cytotoxicity, and biological evaluation of carbohydrate/C-glycoside conjugates are described. The design concept is predicted on the idea that physiological barriers like the blood brain barrier could be crossed selectively by using glucose or glucose derivative/drug conjugates. The study demonstrates that, (1) carbohydrates and C-glycosides can be bonded at nonanomeric positions by the reaction of carbohydrate triflates with C-glycoside alkoxydes in the presence of DMPU; (2) there is a structure-activity relationship between the cytotoxicity of the conjugate and the nature of the carbohydrate residue; and (3) peracetylated hexose keto-C-glycoside conjugates are the most cytotoxic keto-C-glycosides.
Uriel
C
C
Laboratoire de Chimie Organique et Spectroscopique UMR 133 BP 8, Villejuif, France.
Egron
M J
MJ
Santarromana
M
M
Scherman
D
D
Antonakis
K
K
Herscovici
J
J
D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D051272:Glucose Transporter Type 1; D005960:Glucosides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006027:Glycosides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006601:Hexoses / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D008223:Lymphoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D009004:Monosaccharide Transport Proteins / Q000187:drug effects / Q000378:metabolism*; D011753:Pyrones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
C105401:1-(5,6-dihydro-6-(glucopyranosyl)oxymethyl-5-oxo-2H-pyran-2-yl)methylcyclohex-1-ene; C105402:1-(5,6-dihydro-6--(glucopyranos-6-yl)oxymethyl-5-oxo-2H-pyran-2yl)methylcyclohex-1-ene; D051272:Glucose Transporter Type 1; D005960:Glucosides; D006027:Glycosides; D006601:Hexoses; D009004:Monosaccharide Transport Proteins; D011753:Pyrones; C495677:SLC2A1 protein, human; D005947:Glucose