Abstract
Inhibition of acyl CoA:diacylglycerol acyltransferase (DGAT) is proposed to be a drug target for the treatment of obesity and type 2 diabetes. Bioassay-guided fractionation of the CH(2)Cl(2)-soluble extract of the stem bark of Erythrina senegalensis, using an in vitro DGAT enzyme assay, resulted in the isolation of eight known prenylflavonoids, 8-prenylleutone (1), auriculatin (2), erysenegalensein O (3), erysenegalensein D (4), erysenegalensein N (5), derrone (6), alpinumisoflavone (7), and 6,8-diprenylgenistein (8). Compounds 1, 2-4, 6, and 8 inhibited DGAT activity, with IC(50) values ranging from 1.1 +/- 0.3 to 15.1 +/- 1.1 microg/mL. On the basis of the data obtained, we propose isoflavonoids with isoprenyl groups as a novel class of DGAT inhibitors.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anti-Obesity Agents / chemistry
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Anti-Obesity Agents / isolation & purification
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Anti-Obesity Agents / pharmacology*
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Chemical Fractionation
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Diacylglycerol O-Acyltransferase / antagonists & inhibitors*
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / isolation & purification
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Enzyme Inhibitors / pharmacology*
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Erythrina* / chemistry
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Hypoglycemic Agents / chemistry
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Hypoglycemic Agents / isolation & purification
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Hypoglycemic Agents / pharmacology*
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Magnetic Resonance Spectroscopy
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Male
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Mass Spectrometry
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Microsomes, Liver / drug effects
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Microsomes, Liver / enzymology
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Molecular Structure
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Rats
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Rats, Sprague-Dawley
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Spectrophotometry, Ultraviolet
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Structure-Activity Relationship
Substances
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Anti-Obesity Agents
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Enzyme Inhibitors
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Hypoglycemic Agents
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Dgat1 protein, rat
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Diacylglycerol O-Acyltransferase