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Fiziologichnyi Zhurnal - <a id="lj1_ret_bk_to_jl0_href_id" href="?list0=13">Fiziol. Zh. 2011;</a> <a id="lj1_ret_bk_to_jl0_href_id" href="?list1=67">57(6):</a> 31-37
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 acidsensing ion channels

V. A. Sukach, A.Z. Buta, O.P. Maximyuk, D.B. Kovalskyy, M.V. Vovk, O.O. Krishtal.

    Ін-т органічної хімії НАН України, Київ;Ін-т фізіології ім. О.О.Богомольця НАН України, Київ;Міжнар. центр молекул. фізіології НАН України, Київ


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. Машковский М.Д. Лекарственные средства. - 15-е изд., перераб., испр. и доп. М.: Изд-во Новая Волна. -2005. - 1200 с.
  2. 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.
  3. Farinola N., Piller N. Pharmacogenomics: Its role in reestablishing coumarin as treatment for lymphedema // Lymphat. Res. and Biol. - 2005. - 3 (2). - P. 81-86.
  4. Korkushko A.O., Kryshtal O.A. Organic-cation-blocking of proton-induced sodium permeability in the mem­brane of rat trigeminal neurons // Neurophysiology. -1984. - 16, №4. - P. 557-561.
  5. Krishtal O. The ASICs: Signaling molecules? Modulators? // Trends in Neurosci. - 2003. - 26, № 9. - P. 477-483.
  6. 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, № 1. - P. 19-24.
  7. Link K.P. The Discovery of dicumarol and its sequels // Circulation. - 1959. - 19, №1. - P. 97-107.
  8. 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
  9. 9. 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.
  10. 10. 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. - № 1. - P. 25-32. 11. 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 //

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