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

• Published in: Bulletin of experimental biology and medicine Vol. 163; no. 1; p. 54
• Main Authors: Tatyanenko, L V, Shmatko, N Yu, Sanina, N A, Dobrokhotova, O V, Pikhteleva, I Yu, Kotel'nikov, A I, Aldoshin, S M
• Format: Journal Article
• Language: English
• Published: United States 01.05.2017
• Subjects: Adenosine Triphosphate; Animals; Biological Transport - drug effects; Calcium-Transporting ATPases - metabolism; Cyclic Nucleotide Phosphodiesterases, Type 1 - metabolism; Enzyme Activation - drug effects; Ferrous Compounds - chemistry; Ferrous Compounds - pharmacology; Kinetics; Nitro Compounds - chemistry; Nitro Compounds - pharmacology; Rats, Wistar; Sarcoplasmic Reticulum - chemistry; Sarcoplasmic Reticulum - enzymology; cyclic guanosine monophosphate phosphodiesterase; sarcoplasmic reticulum Ca2+-ATPase; nitrosyl iron complexes

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 -ATPase of sarcoplasmic reticulum and cGMP phosphodiesterase. Nitrosyl iron complexes [Fe(C N H S)Cl(NO) ] [Fe(NO) (C N H S) ] Cl (I), [Fe(SC(N(CH ) ) (NO) ]Cl (II), [Fe(SC(NH ) ) (NO) Cl×H O (III), and [Fe(SC(NH ) ) (NO) ] SO ×H O (IV) in a concentration of 10 M completely inhibited the transporting and hydrolytic functions of Ca -ATPase. In a concentration of 10 M, they inhibited active Ca 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 -ATPase (Ki=1.7×10 M). All the studied iron-sulphur complexes in a concentration of 10 M inhibited cGMP phosphodiesterase function. These data suggest that the studied complexes can exhibit antimetastatic, antiaggregation, vasodilatatory, and antihypertensive activities.