Abstract
2-Alkylchromen-4-one 6-O-sulfamates, a new class of potent steroid sulfatase (STS) inhibitors, were evaluated for their estrogenic potential. Structure-activity relationships for estrogenic activity were identified; however, no correlation with STS inhibition was found. Estrogenicity is favored by bulky side chains and can be effectively abrogated by an (additional) linear substituent. Compound 2g, which lacks estrogenicity while potently inhibiting STS, has an ideal in vitro profile for the treatment of breast cancer.
MeSH terms
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Benzopyrans / chemistry
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Benzopyrans / pharmacology*
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Binding, Competitive
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Breast Neoplasms
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Cell Division / drug effects
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Cell Line, Tumor
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Drug Screening Assays, Antitumor
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Estrogen Receptor alpha
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Estrogen Receptor beta
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Estrogens / chemistry
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Estrogens / pharmacology*
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Female
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Fluorescence Polarization
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Humans
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Ligands
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Receptors, Estrogen / drug effects
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Receptors, Estrogen / metabolism
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Steryl-Sulfatase / antagonists & inhibitors
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Structure-Activity Relationship
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Sulfonic Acids / chemistry
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Sulfonic Acids / pharmacology*
Substances
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Benzopyrans
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Enzyme Inhibitors
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Estrogen Receptor alpha
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Estrogen Receptor beta
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Estrogens
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Ligands
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Receptors, Estrogen
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Sulfonic Acids
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sulfamic acid
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Steryl-Sulfatase