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Effect of Iron Nitrosyl Complexes, No Donors, on the Activity of Ca2+-Atpase of Sarcoplasmic Reticulum and Phosphodiesterase of Cyclic Guanosine Monophosphate

  • Molecular-Biological Problems of Drug Design and Mechanism of Drug Action
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Pharmaceutical Chemistry Journal Aims and scope

We studied the effect of iron nitrosyl complexes, NO donors, of various structural types on the activity of Ca2+-ATPase of sarcoplasmic reticulum (SR) and phosphodiesterase (PDE) of cyclic guanosine monophosphate (cGMP). It was established that iron nitrosyl complexes with organic ligands modulate functions of both enzymes. They effectively inhibited the hydrolytic and transport functions of Ca2+-ATPase SR at concentrations 0.1 – 0.01 mM and decoupled ATP hydrolysis and active Ca2+ transport at concentrations 0.01 – 0.0001 mM, thus disrupting the Ca2+ balance in cells. This influenced thrombogenesis and adhesion of metastatic cells to capillary endothelium. The compound [Fe(SC(NH2)2)2(NO)2]2[Fe2(S2O3)2(NO)4] produced non-competitive and reversible inhibition of Ca2+-ATPase SR functioning with K i = 0.70∙10–6 M. All studied iron nitrosyl complexes inhibited the activity of PDE-cGMP, which led to accumulation of cGMP, which is a secondary messenger influencing the in vivo anti-aggregation effect. The obtained results suggested that the studied iron nitrosyl complexes could be considered as potential drugs.

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Authors and Affiliations

  1. Institute of Problems of Chemical Physics, Russian Academy of Sciences, Moscow Oblast, Chernogolovka, 142432, Russia

    L. V. Tat’yanenko, O. V. Dobrokhotova, A. I. Kotel’nikov, N. A. Sanina, G. I. Kozub, T. A. Kondrat’eva & S. M. Aldoshin

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  1. L. V. Tat’yanenko
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  2. O. V. Dobrokhotova
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  3. A. I. Kotel’nikov
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  4. N. A. Sanina
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  5. G. I. Kozub
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  6. T. A. Kondrat’eva
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  7. S. M. Aldoshin
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Correspondence to A. I. Kotel’nikov.

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Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 47, No. 9, pp. 3 – 6, September, 2013.

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Tat’yanenko, L.V., Dobrokhotova, O.V., Kotel’nikov, A.I. et al. Effect of Iron Nitrosyl Complexes, No Donors, on the Activity of Ca2+-Atpase of Sarcoplasmic Reticulum and Phosphodiesterase of Cyclic Guanosine Monophosphate. Pharm Chem J 47, 455–458 (2013). https://doi.org/10.1007/s11094-013-0991-5

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  • DOI: https://doi.org/10.1007/s11094-013-0991-5

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