Inhibition of copper-dependent amine oxidases by some hydrazides of pyrrol-1-ylbenzoic and pyrrol-1-ylphenylacetic acids.
Some hydrazides of pyrrol-1-ylbenzoic and pyrrol-1-ylphenylacetic acids were prepared, and their effect on copper-dependent amine oxidases (Cu-AOs) and FAD monoamine oxidases (MAOs) activities was tested. The compounds were not substrates for Cu-AO enzymes but acted as noncompetitive inhibitors. Hydrazides of pyrrol-1-ylphenylacetic acids were highly specific for plasma amine oxidase (Ki = 0.5-1 microM). In contrast, all the hydrazides were weak inhibitors of MAO activity. Incubation with the hydrazide derivatives led to irreversible inactivation of Cu-AOs. Therefore, the inhibition implied two distinct steps. The first one consisted of the rapid formation of the enzyme-inhibitor complex and was reversed by dialysis. In the second step, the complex was irreversibly transformed, probably by the formation of a Schiff base between the hydrazide and the prosthetic carbonyl group of the enzyme.
D006631:Amine Oxidase (Copper-Containing) / Q000037:antagonists & inhibitors; D000818:Animals; D001921:Brain / Q000201:enzymology; D002417:Cattle; D003300:Copper / Q000378:metabolism*; D005182:Flavin-Adenine Dinucleotide / Q000378:metabolism; D006801:Humans; D006834:Hydrazines / Q000494:pharmacology*; D007538:Isoniazid / Q000494:pharmacology; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000037:antagonists & inhibitors*; D010648:Phenylacetates / Q000138:chemical synthesis / Q000494:pharmacology*; D011758:Pyrroles / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats
D006834:Hydrazines; D008996:Monoamine Oxidase Inhibitors; D010648:Phenylacetates; D011758:Pyrroles; D005182:Flavin-Adenine Dinucleotide; D003300:Copper; D006631:Amine Oxidase (Copper-Containing); D000587:Oxidoreductases Acting on CH-NH Group Donors; D007538:Isoniazid