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Effect of Cyclic Hydroxamic Acids Derived from Glycine and D,L-Alanine on Activity of Ca2+, Mg2+-ATPase Hydrolases of Sarcoplasmic Reticulum and Cyclic Guanosine Monophosphate Phosphodiesterase

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

The effects of cyclic hydroxamic acids (CHAs) derived from glycine and D,L-alanine on the enzymatic activity of Ca2+,Mg2+-ATPase from sarcoplasmic reticulum (Ca2+,Mg2+-ATPase SR) and cyclic guanosine monophosphate phosphodiesterase (PDEcGMP) were investigated. CHAs I (C5H10N2O2), II (C6H12N2O2), III (C8H15N3O2), IV (C9H17N3O2), V (C11H21N3O2), and VI (C12H23N3O2) were modulators of Ca2+,Mg2+-ATPase SR enzyme activity. Compounds I-VI decoupled to various extents the hydrolytic and transport functions of Ca2+,Mg2+-ATPase SR, disrupting the ratio of intra- and extracellular Ca2+ ions. This affected the adhesion of metastatic cells to capillary endothelium. Compounds IV and VI had the highest metastasis inhibition indices (MII%) for B-16 melanoma of 33 and 81%, respectively. This correlated with a decreased Ca2+ transmembrane transfer coefficient into SR vesicles of 0.75 for IV and 0.5 for VI compared with a [Ca2+]/[ATP] ratio in the control of 1.4. CHAs I-VI did not affect the functioning of PDEcGMP. The results enabled potential antimetastatic drugs in the CHA series to be predicted.

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Authors and Affiliations

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

    L. V. Tat’yanenko, N. P. Konovalova, O. V. Dobrokhotova, I. Yu. Pikhteleva, D. V. Mishchenko, B. S. Fedorov & I. V. Vystorop

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  1. L. V. Tat’yanenko
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  2. N. P. Konovalova
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  3. O. V. Dobrokhotova
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  4. I. Yu. Pikhteleva
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  5. D. V. Mishchenko
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  6. B. S. Fedorov
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  7. I. V. Vystorop
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Correspondence to D. V. Mishchenko.

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Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 47, No. 5, pp. 3 – 6, May, 2013.

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Tat’yanenko, L.V., Konovalova, N.P., Dobrokhotova, O.V. et al. Effect of Cyclic Hydroxamic Acids Derived from Glycine and D,L-Alanine on Activity of Ca2+, Mg2+-ATPase Hydrolases of Sarcoplasmic Reticulum and Cyclic Guanosine Monophosphate Phosphodiesterase. Pharm Chem J 47, 235–238 (2013). https://doi.org/10.1007/s11094-013-0935-0

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  • DOI: https://doi.org/10.1007/s11094-013-0935-0

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