Abstract
A series of estrone and estradiol derivatives having an N-butyl,methyl heptanamide side chain at C6-position were synthesized, tested as inhibitors of type 1 17beta-HSD and assessed for their possible estrogenic activity. A better type 1 17beta-HSD inhibition was obtained for the 6beta-side chain orientation over 6alpha; the C17-alcohols are more potent inhibitors than the corresponding ketones; introducing a 2-methoxy group decreased the inhibitory potency; and the replacement of a C-S bond by a C-C bond in the C6beta-side chain is not detrimental to inhibition. Interestingly, the new inhibitors were also found less estrogenic than the lead compound in two breast cancer cell lines, T-47D and MCF-7.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / pharmacology*
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Breast Neoplasms / drug therapy
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Chromatography, Thin Layer
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / pharmacology*
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Estradiol / analogs & derivatives*
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Estradiol / chemical synthesis
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Estradiol / pharmacology*
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Estradiol Dehydrogenases / antagonists & inhibitors*
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Estrone / analogs & derivatives*
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Estrone / chemical synthesis
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Estrone / pharmacology*
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Female
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Humans
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Indicators and Reagents
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Isoenzymes / antagonists & inhibitors
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Mass Spectrometry
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Models, Molecular
Substances
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Antineoplastic Agents
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Enzyme Inhibitors
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Indicators and Reagents
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Isoenzymes
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Estrone
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Estradiol
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Estradiol Dehydrogenases
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HSD17B1 protein, human