Synthesis of O-methylsulfonyl derivatives of D-glucose as potential alkylating agents for targeted drug delivery to the brain. Evaluation of their interaction with the human erythrocyte GLUT1 hexose transporter.
In order to obtain hydrophilic analogues of 1,4-dimethylsulfonyloxybutane (busulfan) with enhanced selectivity and improved brain penetration, we have synthesized 6-O-methylsulfonyl-D-glucose, 3-O-methylsulfonyl-D-glucose, 3,6-di-O-methylsulfonyl-D-glucose, 4-O-methylsulfonyl-D-glucose, and 4,6-di-O-methylsulfonyl-D-glucose, and we have studied their interactions with the human erythrocyte GLUT1 hexose transport system. Mesylation of OH-4 and OH-6 of glucose resulted in a slightly diminished affinity for the GLUT1 glucose transporter, whereas mesylation of OH-3 led to complete loss of affinity.
Halmos
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UMR 133 CNRS/Rhône-Poulenc Rorer, Laboratoire de Chimie Organique Biologique, Villejuif, France.
Santarromana
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Antonakis
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Scherman
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D018906:Antineoplastic Agents, Alkylating / Q000138:chemical synthesis* / Q000494:pharmacology; D001812:Blood-Brain Barrier; D002066:Busulfan / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D004912:Erythrocytes / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D051272:Glucose Transporter Type 1; D006801:Humans; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009004:Monosaccharide Transport Proteins / Q000097:blood* / Q000187:drug effects; D013451:Sulfonic Acids
D018906:Antineoplastic Agents, Alkylating; D051272:Glucose Transporter Type 1; D007202:Indicators and Reagents; D009004:Monosaccharide Transport Proteins; C495677:SLC2A1 protein, human; D013451:Sulfonic Acids; D002066:Busulfan; D005947:Glucose