Effects of Nitrosyl Iron Complexes with Thiocarbamide and Its Aliphatic Derivatives on Activities of Ca 2+ -ATPase of Sarcoplasmic Reticulum and cGMP Phosphodiesterase.

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 Ca ²⁺ -ATPase of sarcoplasmic reticulum and cGMP phosphodiesterase. Nitrosyl iron complexes [Fe(C ₃ N ₂ H ₈ S)Cl(NO) ₂ ] ⁰ [Fe(NO) ₂ (C ₃ N ₂ H ₈ S) ₂ ] ⁺ Cl ^- (I), [Fe(SC(N(CH ₃ ) ₂ ) ₂ (NO) ₂ ]Cl (II), [Fe(SC(NH ₂ ) ₂ ) ₂ (NO) ₂ Cl×H ₂ O (III), and [Fe(SC(NH ₂ ) ₂ ) ₂ (NO) ₂ ] ₂ SO ₄ ×H ₂ O (IV) in a concentration of 10 ^-4 M completely inhibited the transporting and hydrolytic functions of Ca ²⁺ -ATPase. In a concentration of 10 ^-5 M, they inhibited active Ca ²⁺ 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 Ca ²⁺ -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.