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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.

Original publication

DOI

10.1016/j.bmc.2008.11.032

Type

Journal article

Journal

Bioorg Med Chem

Publication Date

15/01/2009

Volume

17

Pages

905 - 918

Keywords

Animals, Arylamine N-Acetyltransferase, Binding Sites, Biomarkers, Tumor, Breast Neoplasms, Enzyme Inhibitors, Female, Humans, Isoenzymes, Mice, Rhodanine, Thiazolidinediones