Inhibition of copper/quinoprotein amine oxidases from Aspergillus niger by benzophenanthridine alkaloids.
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.
Luhová
L
L
Department of Analytical and Organic Chemistry, Faculty of Science, Palacký University, Olomouc, Czech Republic.
Frébort
I
I
Ulrichová
J
J
Adachi
O
O
Simánek
V
V
Pec
P
P
D000470:Alkaloids / Q000494:pharmacology*; D006631:Amine Oxidase (Copper-Containing) / Q000037:antagonists & inhibitors*; D001234:Aspergillus niger / Q000201:enzymology*; D053119:Benzophenanthridines; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007546:Isoquinolines; D010617:Phenanthridines / Q000494:pharmacology*
D000470:Alkaloids; D053119:Benzophenanthridines; D004791:Enzyme Inhibitors; D007546:Isoquinolines; D010617:Phenanthridines; C002066:fagaronine; C005705:sanguinarine; C016299:chelerythrine; D006631:Amine Oxidase (Copper-Containing)