Imidazoacridin-6-ones as novel inhibitors of the quinone oxidoreductase NQO2.
The purpose of the work was to identify novel inhibitors of the enzyme NQO2. Using computational molecular modelling, a QSAR (R(2)=0.88) was established, relating inhibitory potency with calculated binding affinity. From this, the imidazoacridin-6-one, NSC660841, was identified as the most potent inhibitor of NQO2 yet reported (IC(50)=6 nM).
Nolan
K A
KA
School of Pharmacy and Pharmaceutical Sciences, the University of Manchester and Manchester Cancer Research Center, Oxford Road, Manchester M13 9PT, UK.
Humphries
M P
MP
Bryce
R A
RA
Stratford
I J
IJ
D000166:Acridines / Q000737:chemistry* / Q000494:pharmacology; D054831:Acridones / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D020134:Catalytic Domain; D003198:Computer Simulation; D016208:Databases, Factual; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000737:chemistry* / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship; D011808:Quinone Reductases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013816:Thermodynamics
D000166:Acridines; D054831:Acridones; D004791:Enzyme Inhibitors; D007093:Imidazoles; C551000:NSC 660841; C419642:NRH - quinone oxidoreductase2; D011808:Quinone Reductases