Abstract
A new series of coumarin inhibitors of hsp90 lacking the noviose moiety as well as substituents on C-7 and C-8 positions of the aromatic ring was synthesised and their hsp90 inhibitory activity has been delineated: for example, their capacity to induce the degradation of client proteins and to inhibit estradiol-induced transcription in human breast cancer cells. In cell proliferation assay, the most active compound 5g was approximately 8 times more potent than the parent novobiocin natural compound.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antibiotics, Antineoplastic / chemical synthesis
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Antibiotics, Antineoplastic / pharmacology*
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Binding Sites
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Breast Neoplasms / pathology
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Cell Line, Tumor / drug effects
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Cell Proliferation / drug effects*
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Coumarins / chemistry
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Coumarins / pharmacology*
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Drug Screening Assays, Antitumor
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / pharmacology*
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Estradiol / pharmacology
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HSP90 Heat-Shock Proteins / antagonists & inhibitors*
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Humans
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Novobiocin / chemical synthesis
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Novobiocin / pharmacology*
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Structure-Activity Relationship
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Transcription, Genetic / drug effects
Substances
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Antibiotics, Antineoplastic
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Coumarins
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Enzyme Inhibitors
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HSP90 Heat-Shock Proteins
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Novobiocin
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Estradiol