Advertisement

Bulletin of Experimental Biology and Medicine

, Volume 168, Issue 3, pp 330–333 | Cite as

The Effect of Nitroxyalkyl Succinimides on Activity of Cyclic Guanosine Monophosphate Phosphodiesterase

  • L. V. Tat’yanenko
  • O. V. Dobrokhotova
  • M. A. Fadeev
  • A. B. Eremeev
  • A. N. Utyonishev
  • V. V. Tkachev
  • N. S. GoryachevEmail author
  • A. I. Kotelnikov
  • B. S. Fedorov
PHARMACOLOGY AND TOXICOLOGY
  • 5 Downloads

The effect of N-nitroxymethyl succinimide (1), N-(2-nitroxyethyl) succinimide (2) and N-(3-nitroxypropyl) succinimide (3) on enzymatic activity of cyclic guanosine monophosphate (cGMP) phosphodiesterase was studied and crystal structure of compound (2) was determined. It was shown that all studied N-nitroxy succinimides inhibited cGMP phosphodiesterase in a concentration range of 0.1-0.001 mM. Compound (2) noncompetitively and reversibly inhibited hydrolytic function of enzyme with Ki=1.7×10—5 М. Inhibition constant for the reference compound N-(2-nitroethyl) nicotinamide (nicorandil) was 3×10—5 М.

Key Words

cGMP phosphodiesterase N-nitroxyalkyl succinimides inhibition X-ray analysis 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Bailey JL. Techniques in Protein Chemistry. Moscow, 1980. Russian.Google Scholar
  2. 2.
    Berezin IV, Klesov AA. Practical Course of Chemical and Enzymatic Kinetics. Moscow, 1973. Russian.Google Scholar
  3. 3.
    Granik VG, Grigor’iev NB. Nitric Oxide (NO). A New Path to Drug Discovery. Moscow, 2004. Russian.Google Scholar
  4. 4.
    Granik VG, Grigor’ev NB. Exogenous donors of nitric oxide (a chemical aspect). Russ. Chem. Bull. 2002;51(8):1375-1422.CrossRefGoogle Scholar
  5. 5.
    Libinzon RE, Shchekoldina TG, Batolkina OE, Iagniatinskaia AM. Adenosine-3’,5’-monophosphate phosphodiesterase of the cerebral cortex and the effect of cardiovascular preparations. Vopr. Med. Khim. 1977;23(4):526-30. Russian.PubMedGoogle Scholar
  6. 6.
    State Register of Registered Drugs in Russia. Moscow, 2006. Vol. 14. P. 717-718. Russian.Google Scholar
  7. 7.
    Sernov LN, Gatsura VV. A differential indicator method of identifying zones of ischemia and necrosis in rats with experimental myocardial infarction. Bull. Exp. Biol. Med. 1989;107(5):606-608.CrossRefGoogle Scholar
  8. 8.
    Fedorov BS, Bogdanov GN, Fadeev MA, Lagodzinskaya GV. Synthesis and antiischemic activity of dicarboxylic nitroxyalkylamides and nitroxyalkylimides. Russ. Chem. Bull. 2014;63(5):1119-1125.CrossRefGoogle Scholar
  9. 9.
    Sheldrick GM. SHELXTL v. 6.14, Structure Determination Software Suite, Brucker AXS, Madison, Wisconsin, USA, 2000.Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2020

Authors and Affiliations

  • L. V. Tat’yanenko
    • 1
  • O. V. Dobrokhotova
    • 1
  • M. A. Fadeev
    • 1
  • A. B. Eremeev
    • 1
  • A. N. Utyonishev
    • 1
  • V. V. Tkachev
    • 1
  • N. S. Goryachev
    • 1
    • 2
    Email author
  • A. I. Kotelnikov
    • 1
    • 2
  • B. S. Fedorov
    • 1
  1. 1.Institute of Problems of Chemical PhysicsRussian Academy of SciencesChernogolovkaRussia
  2. 2.M. V. Lomonosov Moscow State UniversityMoscowRussia

Personalised recommendations