Effects of Nitrosyl Iron Complexes with Thiocarbamide and Its Aliphatic Derivatives on Activities of Ca2+-ATPase of Sarcoplasmic Reticulum and cGMP Phosphodiesterase

Abstract

We studied the effects of water-soluble cationic dinitrosyl iron complexes with thiocarbamide and its aliphatic derivatives, new synthetic analogs of natural NO donors, active centers of nitrosyl [1Fe-2S]proteins, on activities of Ca²⁺-ATPase of sarcoplasmic reticulum and cGMP phosphodiesterase. Nitrosyl iron complexes [Fe(C₃N₂H₈S)Cl(NO)₂]⁰[Fe(NO)₂(C₃N₂H₈S)₂]⁺Cl^—(I), [Fe(SC(N(CH₃)₂)₂(NO)₂]Cl (II), [Fe(SC(NH₂)₂)₂(NO)₂Cl×H₂O (III), and [Fe(SC(NH₂)₂)₂(NO)₂]₂SO₄×H₂O (IV) in a concentration of 10^—4 M completely inhibited the transporting and hydrolytic functions of Ca²⁺-ATPase. In a concentration of 10^—5 M, they inhibited active Ca²⁺ transport by 57±6, 75±8, 80±8, and 85±9% and ATP hydrolysis by 0, 40±4, 48±5, and 38±4%, respectively. Complex II reversibly and noncompetitively inhibited the hydrolytic function of Ca²⁺-ATPase (Ki=1.7×10^—6 M). All the studied iron—sulphur complexes in a concentration of 10^—4 M inhibited cGMP phosphodiesterase function. These data suggest that the studied complexes can exhibit antimetastatic, antiaggregation, vasodilatatory, and antihypertensive activities.