Abstract
A group of benzamides related to anacardic acid amide CTPB with alkyl chains of defined length were prepared by a five-step sequence starting from 2,6-dihydroxybenzoic acid, and their activities were compared with those reported for the HAT inhibitor anacardic acid (AA). The subset of 4-cyano-3-trifluoromethylphenylbenzamides with shorter chains exhibited activities similar to that of AA, as they behaved as human p300 inhibitors, induced a decrease in histone acetylation levels in immortalized HEK cells, and counteracted the action of the HDAC inhibitor SAHA in MCF7 breast cancer cells. Moreover, an analogue with the shortest alkyl chain induced significant apoptosis at 50 microM in U937 leukemia cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anacardic Acids / chemistry*
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Apoptosis / drug effects
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Benzamides / chemical synthesis*
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Benzamides / chemistry
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Benzamides / pharmacology*
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Cell Cycle / drug effects
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Cell Differentiation / drug effects
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Cell Division / drug effects
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Dose-Response Relationship, Drug
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Drug Screening Assays, Antitumor
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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G2 Phase / drug effects
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Granulocytes / drug effects
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Histone Acetyltransferases / antagonists & inhibitors*
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Histone Acetyltransferases / chemistry
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Humans
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Hydroxamic Acids / pharmacology
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Molecular Structure
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S Phase / drug effects
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Stereoisomerism
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Structure-Activity Relationship
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Tumor Cells, Cultured
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Vorinostat
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p300-CBP Transcription Factors / antagonists & inhibitors
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p300-CBP Transcription Factors / chemistry
Substances
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Anacardic Acids
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Benzamides
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Enzyme Inhibitors
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Hydroxamic Acids
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anacardic acid
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Vorinostat
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Histone Acetyltransferases
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p300-CBP Transcription Factors
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p300-CBP-associated factor