Quinone reductase 2 substrate specificity and inhibition pharmacology

Chem Biol Interact. 2005 Feb 10;151(3):213-28. doi: 10.1016/j.cbi.2005.01.002.


Quinone reductase 2 is a mammalian cytosolic FAD-dependent enzyme, the activity of which is not supported by conventional nicotinamide nucleotides. An endobiotic substrate has never been reported for this enzyme nor a set of molecular tools, such as inhibitors. In the present work, we used the recombinant human enzyme, expressed in CHO cells for the systematic screening of both co-substrates and substrates. The co-substrates survey showed that the natural occurring compound, N-ribosylnicotinamide, was a poor co-substrate. The synthetic N-benzylnicotinamide is a better one compared to any other compounds tested. We found that tetrahydrofolic acid acted as a co-substrate for the reduction of menadione catalysed by quinone reductase 2, although with poor potency (Km approximately 2 mM). Among a series of commercially available quinones, a single one was found to be substrate of quinone reductase 2, in the presence of N-benzyldihydronicotinamide: coenzyme Q0. Finally, we tested a series of 197 flavonoids as potential inhibitors. We found apigenin, genistein or kaempferol as good inhibitor of quinone reductase 2 activity with IC50 in the 100 nM range. These compounds, co-substrate, substrate and inhibitors will permit to better know this enzyme, the role of which is still poorly understood.

MeSH terms

  • Animals
  • CHO Cells
  • Chromatography, High Pressure Liquid
  • Cloning, Molecular
  • Cricetinae
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Flavones / chemistry
  • Flavones / pharmacology*
  • Humans
  • Kinetics
  • Mammals
  • Quinone Reductases / antagonists & inhibitors*
  • Quinone Reductases / metabolism*
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / metabolism
  • Structure-Activity Relationship
  • Substrate Specificity


  • Enzyme Inhibitors
  • Flavones
  • Recombinant Proteins
  • Quinone Reductases