Effects of Nitrosyl Iron Complexes with Thiocarbamide and Its Aliphatic Derivatives on Activities of Ca2+-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 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)(2)ClxH(2)O (III), and [Fe(SC(NH2)(2))(2)(NO)(2)](2)SO(4)xH(2)O (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=1.7x10(-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.