Abstract
We report the synthesis and biochemical evaluation of new competitive inhibitors of the cytosolic (NADH-dependent) glycerophosphate dehydrogenase. The best tested compound, phosphono-propionohydroxamic acid, with a Ki of 6 microM, might be of interest as an anti-obesity drug.
MeSH terms
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Animals
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Cytosol / drug effects
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Cytosol / enzymology*
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / pharmacology*
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Glycerolphosphate Dehydrogenase / antagonists & inhibitors*
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Humans
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Hydrogen Bonding
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Hydroxamic Acids / chemical synthesis*
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Hydroxamic Acids / pharmacology*
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Kinetics
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Magnetic Resonance Spectroscopy
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Molecular Conformation
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Muscle, Skeletal / drug effects
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Muscle, Skeletal / enzymology*
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NAD / metabolism*
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Rabbits
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Spectrometry, Mass, Electrospray Ionization
Substances
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Enzyme Inhibitors
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Hydroxamic Acids
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phosphono-propionohydroxamic acid
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NAD
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Glycerolphosphate Dehydrogenase