Synthesis and in vitro evaluation of novel small molecule inhibitors of bacterial arylamine N-acetyltransferases (NATs).
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.
Brooke
Edward W
EW
Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK.
Davies
Stephen G
SG
Mulvaney
Andrew W
AW
Okada
Minoru
M
Pompeo
Frédérique
F
Sim
Edith
E
Vickers
Richard J
RJ
Westwood
Isaac M
IM
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
D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D001191:Arylamine N-Acetyltransferase