Imidazoacridin-6-ones as novel inhibitors of the quinone oxidoreductase NQO2

Bioorg Med Chem Lett. 2010 May 1;20(9):2832-6. doi: 10.1016/j.bmcl.2010.03.051. Epub 2010 Mar 15.

Abstract

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).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acridines / chemistry*
  • Acridines / pharmacology
  • Acridones / chemistry*
  • Acridones / pharmacology
  • Binding Sites
  • Catalytic Domain
  • Computer Simulation
  • Databases, Factual
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Imidazoles / chemistry*
  • Imidazoles / pharmacology
  • Quantitative Structure-Activity Relationship
  • Quinone Reductases / antagonists & inhibitors*
  • Quinone Reductases / metabolism
  • Thermodynamics

Substances

  • Acridines
  • Acridones
  • Enzyme Inhibitors
  • Imidazoles
  • NSC 660841
  • NRH - quinone oxidoreductase2
  • Quinone Reductases