Abstract
A high throughput screen for inhibitors of the oncogenic transcription factor activator protein-1 (AP-1) was applied to the NCI repository of natural product extracts. The liphophilic extract of the plant Nothospondias staudtii (Simaroubaceae) displayed significant AP-1 inhibition. Bioassay-guided fractionation of the extract lead to a new quassinoid named nothospondin (1), and the known compound glaucarubinone (2). The structure of 1 was elucidated by spectroscopic methods. Compounds 1 and 2 showed potent, dose-dependent AP-1 inhibition at noncytotoxic concentrations.
Published by Elsevier Ltd.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, N.I.H., Intramural
MeSH terms
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Cameroon
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Coumarins / chemistry*
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Coumarins / isolation & purification
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Coumarins / pharmacology
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Magnetic Resonance Spectroscopy
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Molecular Conformation
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Phenanthrenes / chemistry*
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Phenanthrenes / isolation & purification
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Phenanthrenes / pharmacology
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Plant Extracts / chemistry
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Plant Extracts / isolation & purification
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Plant Extracts / pharmacology
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Simaroubaceae / chemistry*
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Transcription Factor AP-1 / antagonists & inhibitors*
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Transcription Factor AP-1 / metabolism
Substances
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Coumarins
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Phenanthrenes
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Plant Extracts
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Transcription Factor AP-1
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nothospondin