Abstract
The identification, synthesis and evaluation of a series of rhodanine and thiazolidin-2,4-dione derivatives as selective inhibitors of human arylamine N-acetyltransferase 1 and mouse arylamine N-acetyltransferase 2 is described. The most potent inhibitors identified have submicromolar activity and inhibit both the recombinant proteins and human NAT1 in ZR-75 cell lysates in a competitive manner. (1)H NMR studies on purified mouse Nat2 demonstrate that the inhibitors bind within the putative active site of the enzyme.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Arylamine N-Acetyltransferase / antagonists & inhibitors*
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Binding Sites
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Biomarkers, Tumor / antagonists & inhibitors
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Breast Neoplasms / drug therapy*
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Breast Neoplasms / pathology
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Enzyme Inhibitors
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Female
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Humans
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Isoenzymes / antagonists & inhibitors*
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Mice
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Rhodanine / chemical synthesis*
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Rhodanine / pharmacology
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Thiazolidinediones / chemical synthesis*
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Thiazolidinediones / pharmacology
Substances
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Biomarkers, Tumor
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Enzyme Inhibitors
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Isoenzymes
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Thiazolidinediones
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thiazolidine-2,4-dione
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Rhodanine
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Arylamine N-Acetyltransferase
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N-acetyltransferase 1
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Nat2 enzyme, mouse