title: Selective small molecule inhibitors of the potential breast cancer marker, human arylamine N-acetyltransferase 1, and its murine homologue, mouse arylamine N-acetyltransferase 2.
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.
authors.affiliation: Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK.
authors.forename: Angela J
authors.initials: AJ
authors.lastname: Russell
authors.forename: Isaac M
authors.initials: IM
authors.lastname: Westwood
authors.forename: Matthew H J
authors.initials: MH
authors.lastname: Crawford
authors.forename: James
authors.initials: J
authors.lastname: Robinson
authors.forename: Akane
authors.initials: A
authors.lastname: Kawamura
authors.forename: Christina
authors.initials: C
authors.lastname: Redfield
authors.forename: Nicola
authors.initials: N
authors.lastname: Laurieri
authors.forename: Edward D
authors.initials: ED
authors.lastname: Lowe
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Davies
authors.forename: Edith
authors.initials: E
authors.lastname: Sim
mesh_terms: D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000037:antagonists & inhibitors*; D001665:Binding Sites; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004791:Enzyme Inhibitors; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D051379:Mice; D012236:Rhodanine / Q000138:chemical synthesis* / Q000494:pharmacology; D045162:Thiazolidinediones / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D014408:Biomarkers, Tumor; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D045162:Thiazolidinediones; C500090:thiazolidine-2,4-dione; D012236:Rhodanine; D001191:Arylamine N-Acetyltransferase; C089384:N-acetyltransferase 1; C524206:Nat2 enzyme, mouse