Abstract
Glycogen utilization involves glycogen phosphorylase, an enzyme which appears to be a potential target for the regulation of glycaemia, as the liver isoform is a major player for hepatic glucose output. A single C-glucosylated malonitrile allowed for the synthesis of three glucose-based derivatives namely bis-oxadiazoles, bis-amides and a C-glucosylated tetrahydropyrimidin-2-one. When evaluated as glycogen phosphorylase inhibitors, two of the synthesized compounds displayed inhibition in the sub-millimolar range. In silico studies revealed that only one out of the bis-amides obtained and the C-glucosylated tetrahydropyrimidin-2-one may bind at the catalytic site.
Copyright © 2012 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Binding Sites / drug effects
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Carbohydrates / chemistry*
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Dose-Response Relationship, Drug
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Glycogen Phosphorylase, Muscle Form / antagonists & inhibitors*
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Glycogen Phosphorylase, Muscle Form / isolation & purification
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Glycogen Phosphorylase, Muscle Form / metabolism
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Glycosylation
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Models, Molecular
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Molecular Structure
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Muscle, Skeletal / enzymology
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Nitriles / chemical synthesis
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Nitriles / chemistry
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Nitriles / pharmacology*
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Rabbits
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Structure-Activity Relationship
Substances
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Carbohydrates
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Enzyme Inhibitors
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Nitriles
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dicyanmethane
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Glycogen Phosphorylase, Muscle Form