Effect of nitrosyl iron complexes and their thio ligands on the activity of phosphodiesterase and sarcoplasmic reticulum Ca2+-ATPase

The effect of certain NO donors, viz., nitrosyl iron complexes (NICs) and their functional thio ligands, on the activity of hydrolytic enzymes was studied taking cyclic guanosine monophosphate phosphodiesterase (cGMP PDE) and sarcoplasmic reticulum (SR) Ca2+-ATPase as examples. It was shown that mononuclear dinitrosyl complexes with 4-nitrophenyl- and 5-nitropyridin-2-ylthiols as well as the binuclear tetranitrosyl complex with 3-hydroxyphenylthiol competitively inhibit the cGMP PDE action with the inhibition constants, Ki, equal to 2.3 · 10−6, 1.0 · 10−4, and 8.7 · 10−5 mol L−1, respectively, and non-competitively inhibit the function of SR Ca2+-ATPase with Ki = 7.4 · 10−5, 7.9 · 10−5 and 1.1 · 10−5 mol L−1, respectively. The thio ligands of the complexes have little effect on the enzyme activity or do not affect it at all. The results obtained make it possible to predict the antihypertensive, antiaggregatory, and vasodilatory activities of the compounds studied.