The effect of nitroxyalkyl derivatives of fullerenylproline methyl ester on the enzymatic activity of Ca 2+ -ATPase of sarcoplasmic reticulum (SR) has been studied. It is shown that hybrid derivatives of C 60 fullerene are capable of inhibiting the activity of Ca 2+ -ATPase of SR. The mononitrate inhibits the hydrolytic activity of the enzyme with K i = 1.92´10 -6 M; active Ca 2+ transport, with K i = 3.79´10 -6 M. The dinitrate inhibits ATP hydrolysis with K i = 2.38´10 -8 M; Ca 2+ transport, with K i = 3.08´10 -8 M. Fullerenylproline methyl ester does not affect the enzymatic activity of Ca 2+ -ATPase. Based on these data it is possible to predict the possible fields of application for hybrid fullerene derivatives as potential drugs.
The effect of iron nitrosyl complexes, NO donors, of a general formula [Fe(L)(NO)] with functional sulfur-containing ligands (L-3-nitro-phenol-2-yl, 4-nitro-phenol-2-yl, or 1-methyl-tetrazol-5-yl) on the activity of sarcoplasmic reticulum Ca-ATPase and cyclic guanosine monophosphate phosphodiesterase (cGMP PDE) was studied. The test complexes uncoupled the hydrolytic and transport functions of Ca- ATPase, thus disturbing the balance of Ca ions in cells, which may affect the formation of thrombi and adhesion of metastatic cells to the endothelium of capillaries. They also inhibited the activity of cGMP PDE, thereby contributing to the accumulation of the second messenger cGMP. The studied iron nitrosyl complexes can be considered as potential drugs.
We have studied the effect of some NO donors based on new nitrosyl iron-sulfur complexes, including the anionic thiosulfate complex Na 2 [Fe 2 (S 2 O 3 ) 2 (NO) 4 ](4H 2 O (I) and neutral thiolate complexes of the general formula [Fe 2 (SR) 2 (NO) 2 ] with R = 1-methylimidazol-2-yl (II), 3-amino-1,2,4-triazol-5-yl (III), and phenyl (IV), on the enzymatic activity of two hydrolytic enzymes, namely, cyclic guanosine monophosphate phosphodiesterase (cGMP PDEase) and Ca 2+ -Mg 2+ -dependent ATPase of sarcoplasmatic reticulum (SR Ca 2+ -ATPase). It has been found that all tested compounds in the concentration range 0.1 -0.001 mM inhibit functioning of cGMP PDEase and SR Ca 2+ -ATPase. Compounds I and II inhibit the activity of cGMP PDEase with K i = 1 and 5 mM, respectively. These compounds are more efficient than the reference drug nicorandil (K i = 0.1 mM) used in clinical therapy. The inhibition of cGMP PDEase functioning favors the accumulation of cGMP, a secondary messenger in living organisms that is responsible for vasodilatory, antiaggregant, and antihypertensive properties of drugs. Inhibition of SR Ca 2+ -ATPase blocks active transport of Ca 2+ ions, thus affecting the equilibrium of Ca ions in cells and the manifestation of the above pharmacological effects. The experimental data allow one to predict the mechanisms of action of chemical compounds under consideration as potential drugs.
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