Українська Русский English

ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2011; 57(6): 31-37


(3-carboxamidino-2-oxo-2H-chromen-7-yl)-4-guanidinobenzoates are novel blockers of pH-sensitive ion channels

Sukach VA, Buta AZ, Maksymiuk OP, Koval's'kyĭ DB, Vovk MV, Kryshtal' OO

  1. Institute of Organic Chemistry of NAS of Ukraine, Kyiv, Ukraine
  2. O.O.Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
  3. International Center Molecular Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
DOI: https://doi.org/10.15407/fz57.06.031

Abstract

Ischemic stroke is one of the most severe brain pathologies that is extremely difficult to treat. Recently it has been found that acidosis accompanying cerebral ischemia induces activa­tion of acid-sensing ion channel ASIC1a which results in its turn in the neuronal death. Here we present novel derivatives of 3-carboxamidinocoumarines that effectively inhibit ASIC1a and ASIC3 channels in concentration-dependent manner. The most active compound inhibits ASIC1a and ASIC3 channels with corresponding IC50 of 7.3 and 13.2 uM. Our data suggest that 3-carboxamidinocoumarines can be used as a scaffold for novel type of highly efficient anti-ischemic drugs.

Keywords: 3-амидино-7-гидроксикумарины,блокаторы рН-чувствительных ионных каналов, антиише-мические препараты.

References

  1. Mashkovsky M.D. Medicines. 15th ed., Revised, ed. and ext. M .: New Wave Publishing House. 2005. 1200 p.
  2.  
  3. Escoubas P., Bernard C., Lambeau G., Lazdunski M., Darbon H. Recombinant production and solution struc­ture of PcTx1, the specific peptide inhibitor of ASIC1a proton-gated cation channels . Protein Sci. 2003. 12. P. 1332-1343. CrossRef PubMed PubMedCentral
  4.  
  5. Farinola N., Piller N. Pharmacogenomics: Its role in reestablishing coumarin as treatment for lymphedema . Lymphat. Res. and Biol. 2005. 3 (2). P. 81-86. CrossRef PubMed
  6.  
  7. Korkushko A.O., Kryshtal O.A. Organic-cation-blocking of proton-induced sodium permeability in the mem­brane of rat trigeminal neurons . Neurophysiology. 1984. 16, N 4. P. 557-561.
  8.  
  9. Krishtal O. The ASICs: Signaling molecules? Modulators? . Trends in Neurosci. 2003. 26, N 9. P. 477-483. CrossRef  
  10. Kuduk S.D., Di Marco C.N., Bodmer-Narkevitch V., Cook S.P., Cato M.J., Jovanovska A., Urban M.O., Leitl M., Sain N., Liang A., Spencer R.H., Kane S.A., Hartman G.D., Bilodeau M.T. Synthesis, structure activity relationship, and pharmacological profile of analogs of the ASIC-3 inhibitor A-317567 . ACS Chem. Neurosci. 2010. 1, N 1. P. 19-24. CrossRef PubMed PubMedCentral
  11.  
  12. Link K.P. The Discovery of dicumarol and its sequels . Circulation. 1959. 19, N 1. P. 97-107. CrossRef PubMed
  13.  
  14. Pignataro G., Simon R.P., Xiong Z. G. Prolonged activation of ASIC1a and the time window for neuropro­tection in cerebral ischaemia . Brain 2007. 130. P.151-158. CrossRef PubMed
  15.  
  16. Ugawa S., Ishida Y., Ueda T., Inoue K., Nagao M., Shimada S. Nafamostat mesilate reversibly blocks acid-sensing ion channel currents. . Biochem. Biophys. Res. Commun. 2007. 363. P. 203-208. CrossRef PubMed
  17.  
  18. Xiong Z.-G., Pignataro G., Li M., Chang S.Y., Simon R.P. Acid-sensing ion channels (ASICs) as pharmaco-logical targets for neurodegenerative diseases . Curr. Opinion in Pharm. 2008. 8. N 1. P. 25-32. CrossRef PubMed PubMedCentral
  19.  
  20. Xiong Z.-G., Zhu X.-M., Chu X.-P., Minami M., Hey J., Wemmie J.A., Price M., Welsh M.J., Simon R.P. Neuroprotection in ischemia: blocking calcium-perme­able acid-sensing ion channels .

© National Academy of Sciences of Ukraine, Bogomoletz Institute of Physiology, 2014-2020.