Abstract
The incidence of obesity and other diseases associated with an increased triacylglycerol mass is growing rapidly, particularly in the United States. Glycerol 3-phosphate acyltransferase (GPAT) catalyzes the rate-limiting step of glycerolipid biosynthesis, the acylation of glycerol 3-phosphate with saturated long-chain acyl-CoAs. In an effort to produce small molecule inhibitors of this enzyme, a series of benzoic and phosphonic acids was designed and synthesized. In vitro testing of this series has led to the identification of several compounds, in particular 2-(nonylsulfonamido)benzoic acid (15g), possessing moderate GPAT inhibitory activity in an intact mitochondrial assay.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Acylation
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Animals
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Drug Design
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Drug Evaluation, Preclinical
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Glycerides / biosynthesis
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Glycerol-3-Phosphate O-Acyltransferase / antagonists & inhibitors*
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Glycerophosphates / metabolism
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Mice
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Mitochondria / enzymology
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Mitochondria / metabolism
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Obesity / drug therapy*
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Organophosphonates / chemical synthesis*
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Organophosphonates / pharmacology
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Structure-Activity Relationship
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Sulfonamides / chemical synthesis*
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Sulfonamides / pharmacology
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ortho-Aminobenzoates / chemical synthesis*
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ortho-Aminobenzoates / pharmacology
Substances
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2-(nonylsulfonamido)benzoic acid
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Glycerides
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Glycerophosphates
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Organophosphonates
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Sulfonamides
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ortho-Aminobenzoates
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alpha-glycerophosphoric acid
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Glycerol-3-Phosphate O-Acyltransferase