Abstract
Madurahydroxylactone (MHL) is a secondary metabolite produced by the soil bacterium Nonomuria rubra and belongs to the family of benzo[a]naphthacenequinones. We report the initial results and structure-activity relationships of our study into a series of thiosemicarbazone derivatives of madurahydroxylactone as potential nonsteroidal inhibitors of the enzyme estrone sulfatase. The most active compound, the cyclohexylthiosemicarbazone, was shown to be a non-competitive inhibitor with a K(i) of 0.35microM. This compound is devoid of estrogenic properties and showed low acute toxicity in the hen's fertile egg screening test.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cytosine / analogs & derivatives
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Cytosine / chemical synthesis*
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Cytosine / pharmacology
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Drug Design
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / pharmacology
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Kinetics
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Lactones / chemical synthesis*
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Lactones / pharmacology
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Naphthacenes / chemical synthesis*
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Naphthacenes / pharmacology
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Purines / chemical synthesis*
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Purines / pharmacology
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Quinones / chemical synthesis*
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Quinones / pharmacology
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Structure-Activity Relationship
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Sulfatases / antagonists & inhibitors*
Substances
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6-methoxypurine
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Enzyme Inhibitors
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Lactones
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Naphthacenes
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Purines
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Quinones
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pseudoisocytosine
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Cytosine
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Sulfatases
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estrone sulfatase