Effect of nitrosyl iron–sulfur complexes on the activity of hydrolytic enzymes

Abstract

We have studied the effect of some NO donors based on new nitrosyl iron—sulfur complexes, including the anionic thiosulfate complex Na 2 [Fe 2 (S 2 O 3 ) 2 (NO) 4 ](4H 2 O (I) and neutral thiolate complexes of the general formula [Fe 2 (SR) 2 (NO) 2 ] with R = 1-methylimidazol-2-yl (II), 3-amino-1,2,4-triazol-5-yl (III), and phenyl (IV), on the enzymatic activity of two hydrolytic enzymes, namely, cyclic guanosine monophosphate phosphodiesterase (cGMP PDEase) and Ca 2+ —Mg 2+ -dependent ATPase of sarcoplasmatic reticulum (SR Ca 2+ —ATPase). It has been found that all tested compounds in the concentration range 0.1 - 0.001 mM inhibit functioning of cGMP PDEase and SR Ca 2+ —ATPase. Compounds I and II inhibit the activity of cGMP PDEase with K i = 1 and 5 μM, respectively. These compounds are more efficient than the reference drug nicorandil (K i = 0.1 mM) used in clinical therapy. The inhibition of cGMP PDEase functioning favors the accumulation of cGMP, a secondary messenger in living organisms that is responsible for vasodilatory, antiaggregant, and antihypertensive properties of drugs. Inhibition of SR Ca 2+ —ATPase blocks active transport of Ca 2+ ions, thus affecting the equilibrium of Ca ions in cells and the manifestation of the above pharmacological effects. The experimental data allow one to predict the mechanisms of action of chemical compounds under consideration as potential drugs.