title: Synthesis and in vitro evaluation of novel small molecule inhibitors of bacterial arylamine N-acetyltransferases (NATs).
abstract: The synthesis and inhibitory activity of a series of 5-substituted-(1,1-dioxo-2,3-dihydro-1H-1 lambda(6)-benzo[e][1,2]thiazin-4-ylidene)-thiazolidine-2,4-dione derivatives as competitive inhibitors of recombinant bacterial arylamine-N-acetyltransferases (NATs) are described. The most potent NAT inhibitors are those that contain planar hydrophobic substituents on the sultam nitrogen.
authors.affiliation: Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK.
authors.forename: Edward W
authors.initials: EW
authors.lastname: Brooke
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Davies
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Mulvaney
authors.forename: Minoru
authors.initials: M
authors.lastname: Okada
authors.forename: Frédérique
authors.initials: F
authors.lastname: Pompeo
authors.forename: Edith
authors.initials: E
authors.lastname: Sim
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Vickers
authors.forename: Isaac M
authors.initials: IM
authors.lastname: Westwood
mesh_terms: D000478:Alkylation; D001191:Arylamine N-Acetyltransferase / Q000037:antagonists & inhibitors*; D001419:Bacteria / Q000187:drug effects / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D007202:Indicators and Reagents; D007700:Kinetics; D008958:Models, Molecular; D008968:Molecular Conformation; D020102:Mycobacterium smegmatis / Q000187:drug effects / Q000201:enzymology; D012486:Salmonella typhimurium / Q000187:drug effects / Q000201:enzymology; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D001191:Arylamine N-Acetyltransferase