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Design and synthesis of small molecule glycerol 3-phosphate acyltransferase inhibitors.

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.

SUBMITTER: Wydysh EA

PROVIDER: S-EPMC3184552 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature

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Design and synthesis of small molecule glycerol 3-phosphate acyltransferase inhibitors.

Wydysh Edward A EA Medghalchi Susan M SM Vadlamudi Aravinda A Townsend Craig A CA

Journal of medicinal chemistry 20090501 10

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 ...[more]

PMID: 19388675

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