Abstract
The rocaglates/rocaglamides are a class of natural products known to display potent anticancer activity. One such derivative, silvestrol, has shown activity comparable to taxol in certain settings. Here, we report the synthesis of various rocaglamide analogues and identification of a hydroxamate derivative (-)-9 having activity similar to silvestrol in vitro and ex vivo for inhibition of protein synthesis. We also show that (-)-9 synergizes with doxorubicin in vivo to reduce Eμ-Myc driven lymphomas.
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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Animals
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology
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Benzofurans / chemical synthesis*
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Benzofurans / chemistry
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Benzofurans / pharmacology
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Cell Line, Tumor
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Cell Survival / drug effects
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Doxorubicin / pharmacology
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Drug Screening Assays, Antitumor
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Drug Synergism
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Eukaryotic Initiation Factor-4F / antagonists & inhibitors
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Humans
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Hydroxamic Acids / chemical synthesis*
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Hydroxamic Acids / chemistry
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Hydroxamic Acids / pharmacology
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Lymphoma / drug therapy
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Lymphoma / pathology
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Mice
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Mice, Inbred C57BL
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Microsomes, Liver / metabolism
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Protein Subunits / antagonists & inhibitors
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Protein Synthesis Inhibitors / chemical synthesis*
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Protein Synthesis Inhibitors / chemistry
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Protein Synthesis Inhibitors / pharmacology
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Stereoisomerism
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Structure-Activity Relationship
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Triterpenes / pharmacology
Substances
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Antineoplastic Agents
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Benzofurans
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Eukaryotic Initiation Factor-4F
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Hydroxamic Acids
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N-methoxy rocaglamide
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Protein Subunits
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Protein Synthesis Inhibitors
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Triterpenes
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silvestrol
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Doxorubicin
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rocaglamide