Abstract
An epoxybenzoquinone, 4-hydroxyphenoxypropionic acid, and 2-hydroxy-3-phenyl-3-butenoic acid derivatives have been designed, synthesized, and evaluated for in vitro inhibition activity against 4-hydroxyphenylpyruvate dioxygenase (4-HPPD) from pig liver by the spectrophotometric enol-borate method. The biological data demonstrated that neither epoxybenzoquinone ester nor 2-hydroxy-3-phenyl-3-butenoic acid is an inhibitor of 4-HPPD. The most potent 4-HPPD inhibitor tested was 3-hydroxy-4-phenyl-2(5H)-furanone with an IC(50) value of 0.5 microM, which may serve as a lead compound for further design of more potent 4-HPPD inhibitors.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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4-Hydroxyphenylpyruvate Dioxygenase / antagonists & inhibitors*
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4-Hydroxyphenylpyruvate Dioxygenase / chemistry
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Animals
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Benzoquinones / chemical synthesis*
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Benzoquinones / chemistry
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Benzoquinones / pharmacology
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Butyrates / chemical synthesis*
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Butyrates / chemistry
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Butyrates / pharmacology
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Drug Design
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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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Epoxy Compounds / chemical synthesis
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Epoxy Compounds / chemistry
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Epoxy Compounds / pharmacology
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Inhibitory Concentration 50
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Lactones / chemical synthesis
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Lactones / chemistry
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Lactones / pharmacology
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Liver / enzymology
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Magnetic Resonance Spectroscopy
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Phenoxyacetates / chemical synthesis*
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Phenoxyacetates / chemistry
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Phenoxyacetates / pharmacology
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Phenylpyruvic Acids / chemistry
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Phenylpyruvic Acids / metabolism
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Swine
Substances
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Benzoquinones
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Butyrates
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Enzyme Inhibitors
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Epoxy Compounds
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Lactones
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Phenoxyacetates
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Phenylpyruvic Acids
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4-hydroxyphenylpyruvic acid
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4-hydroxyphenoxyacetic acid
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4-Hydroxyphenylpyruvate Dioxygenase