Inhibition of copper amine oxidases by pyridine-derived aldoximes and ketoximes

摘要: Abstract The reactions of pea diamine oxidase (PSAO) and 2-phenylethylamine from Arthrobacter globiformis (AGAO) with pyridine-derived oximes were studied. Pyridine carbaldoximes alkyl pyridyl ketoximes act as strong non-competitive inhibitors the enzymes. inhibition constants Ki these compounds vary between 10-4 10-5 M, for AGAO some studied found even micromolar values. presence pyridine moiety in has remarkable influence on potency. Elementary lacking heterocyclic ring, i.e., aliphatic (acetone oxime), alicyclic (cyclohexanone oxime) aromatic (benzaldoxime), are considerably weaker (Ki ∼10-3 or 10-2 M). position ring substitution by –C(R)=NOH group does not play a significant role potency oxime compounds. If nitrogen is quaternised (in hydroxyiminomethyl-1-methylpyridinium iodides), compound looses its inhibitory properties. Extended length substituents ketoxime increases value. enzyme-bound copper represents one possible target sites inhibitors. addition an carbaldoxime to native PSAO sample perturbs absorption spectrum enzyme (by increase region 300–400 nm) that observed reacted apoenzyme. However, additional formation hydrogen bonds amino acid side-chains at active site should be considered, namely 3- 4-substituted derivatives.