Inhibition of copper/quinoprotein amine oxidases from Aspergillus niger by benzophenanthridine alkaloids

J Enzyme Inhib. 1995;9(4):295-302. doi: 10.3109/14756369509036558.

Abstract

Inhibition of copper/quinoprotein amine oxidases (EC 1.4.3.6), AO-I (dimer 2 x 75 kDa) and AO-II (monomer 80 kDa), from the fungus Aspergillus niger by benzophenanthridine alkaloids sanguinarine, chelerythrine, and fagaronine were studied. For both amine oxidases the alkaloids showed reversible noncompetitive inhibition of n-hexylamine oxidation with Ki 0.6, 0.9 and 2.8 mM for sanguinarine, chelerythrine, and fagaronine, respectively. The values of the inhibition constants corresponded to pKR+ values for the iminium ion/pseudobase equilibrium of the alkaloids. Since thio-compounds protected the enzymes against this inhibition, the inhibition effect was ascribed to the interaction with a sulfhydryl group essential for the enzymatic activity.

MeSH terms

  • Alkaloids / pharmacology*
  • Amine Oxidase (Copper-Containing) / antagonists & inhibitors*
  • Aspergillus niger / enzymology*
  • Benzophenanthridines
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology
  • Isoquinolines
  • Phenanthridines / pharmacology*

Substances

  • Alkaloids
  • Benzophenanthridines
  • Enzyme Inhibitors
  • Isoquinolines
  • Phenanthridines
  • fagaronine
  • sanguinarine
  • chelerythrine
  • Amine Oxidase (Copper-Containing)