Abstract
Beta-lactam derivatives of orlistat were prepared and their inhibitory activities toward the thioesterase domain of fatty acid synthase (FAS-TE) were evaluated using a recombinant form of the enzyme. While in general these derivatives showed lower potency compared to beta-lactones, a reasonably potent, lead compound (-)-9 (IC(50)=8.6microM) was discovered that suggests that this class of compounds should be evaluated further.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Anti-Obesity Agents / chemical synthesis
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Anti-Obesity Agents / pharmacology*
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / pharmacology*
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Binding Sites
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / pharmacology*
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Fatty Acid Synthases / antagonists & inhibitors*
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Humans
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Inhibitory Concentration 50
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Lactones / chemistry
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Lactones / pharmacology*
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Models, Chemical
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Orlistat
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Stereoisomerism
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Structure-Activity Relationship
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beta-Lactams / chemical synthesis
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beta-Lactams / pharmacology*
Substances
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Anti-Obesity Agents
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Antineoplastic Agents
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Enzyme Inhibitors
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Lactones
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beta-Lactams
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Orlistat
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Fatty Acid Synthases