Copper complexes with nitronylnitroxyl radicals as lipoxygenase inhibitors with antioxidant activity
The effects of the complexes Cu(L R H) 2 (NO 3 ) 2 (R = H, Me) with the nitronylnitroxyl radicals LRH on the lipoxygenase (LOX-1) activity upon peroxidation of linoleic acid were studied. The complexes under study are reversible enzyme inhibitors, competitive and non-competitive inhibition type being observed for the complex with the methyl-substituted and unsubstituted ligands, respectively. The results of molecular docking showed that the complexes under study are incorporated into the hydrophobic pocket of the LOX-1 active site and the change in the type of inhibition can be explained by introduction of additional methyl group into the imidazole fragment of the ligand, which provides a slightly more favorable interaction of the inhibitor with the enzyme and results in the non-competitive mechanism of inhibition. The starting diamagnetic compounds (L R H 2 ), nitronylnitroxyl radicals (L R H), and Cu II complexes exhibit high activity in the nonenzymatic peroxidation of linoleic acid, as well as in generation of the superoxide radical anion O 2 ·− in the xanthine-xanthine oxidase system.