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Modifications on the carboxylic function of kynurenic acid

  • Basic Neurosciences, Genetics and Immunology - Original Article
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Abstract

Pharmacological and histological studies of ten new amides of kynurenic acid revealed that N-(2-N,N-dimethylaminoethyl)-4-oxo-1H-quinoline-2-carboxamide hydrochloride has effective neuroprotective properties. Namely, this molecule is: (1) proved to be an effective inhibitor of excitatory synaptic transmission in the CA1 region of the hippocampus both in in vitro and ex vivo studies, (2) in four vessel occlusion model of transient global forebrain ischaemia, measuring the rate of hippocampal CA1 pyramidal cell loss and preservation of long-term potentiation at Schaffer collateral-CA1 synapses, the neuroprotective potential was represented. N-(2-N,N-dimethylaminoethyl)-4-oxo-1H-quinoline-2-carboxamide hydrochloride administration significantly diminished hippocampal CA1 cell loss and preserved LTP expression.

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References

  • Borza I, Horvath C, Farkas S, Nagy J, Kolok S (2006) Kynurenic acid amide derivatives as NR2B receptor antagonists. WO2006010967

  • Borza I, Kolok S, Galgoczy K, Gere A, Horvath C, Farkas S, Greiner I, Domany G (2007) Kynurenic acid amides as novel NR2B selective NMDA receptor antagonists. Bioorg Med Chem Lett 17:406–409

    Article  PubMed  CAS  Google Scholar 

  • Drieu K (1986) Preparation and definition of Ginkgo biloba extract. Presse Med 15:1455–1457

    PubMed  CAS  Google Scholar 

  • Fülöp F, Szatmári I, Vámos E, Zádori D, Toldi J, Vecsei L (2009) Syntheses, transformations and pharmaceutical applications of kynurenic acid derivatives. Curr Med Chem 16:4828–4842

    Article  PubMed  Google Scholar 

  • Gellért L, Göblös A, Sárközi K, Fuzik J, Kis Z, Farkas T, Szatmári I, Fülöp F, Vecsei L, Toldi J (2011) Neuroprotection with a new kynurenic analogue. Eur J Pharmacol 667:182–187

    Article  PubMed  Google Scholar 

  • Gigler G, Szenasi G, Simo A, Levay G, Harsing LG Jr, Sas K, Vecsei L, Toldi J (2007) Neuroprotective effect of L-kynurenine sulfate administered before focal cerebral ischemia in mice and global cerebral ischemia in gerbils. Eur J Pharmacol 564:116–122

    Article  PubMed  CAS  Google Scholar 

  • Giles GI, Collins CA, Stone TW, Jacob C (2003) Electrochemical and in vitro evaluation of the redox properties of kynurenine species. Biochem Biophys Res Commun 300:719–724

    Article  PubMed  CAS  Google Scholar 

  • Hilmas C, Pereira EF, Alkondon M, Rassoulpour A, Schwarcz R, Albuquerque EX (2001) The brain metabolite kynurenic acid inhibits alpha7 nicotinic receptor activity and increases non-alpha7 nicotinic receptor expression: physiopathological implications. J Neurosci 21:7463–7473

    PubMed  CAS  Google Scholar 

  • Huse H, Whiteley M (2011) 4-Quinolones: smart phones of the microbial world. Chem Rev 111:152–159

    Article  PubMed  CAS  Google Scholar 

  • Luchowska E, Luchowski P, Sarnowska A, Wielosz M, Turski WA, Urbanska EM (2003) Endogenous level of kynurenic acid and activities of kynurenine aminotransferases following transient global ischemia in the gerbil hippocampus. Pol J Pharmacol 55:443–447

    PubMed  CAS  Google Scholar 

  • Moroni F (1999) Tryptophan metabolism and brain function: focus on kynurenine and other indole metabolites. Eur J Pharmacol 375:87–100

    Article  PubMed  CAS  Google Scholar 

  • Nagy K, Plangár I, Gellért L, Demeter I, Farkas T, Kis Z, Marosi M, Zádori D, Klivényi P, Fülöp F, Szatmári I, Vecsei L, Toldi J (2011) Molecular structures and functions: comparative studies of some kynurenic acid analogs. J Neural Transm (under publication)

  • Nemeth H, Toldi J, Vecsei L (2005) Role of kynurenines in the central and peripheral nervous systems. Curr Neurovasc Res 2:249–260

    Article  PubMed  Google Scholar 

  • Nemeth H, Toldi J, Vecsei L (2006) Kynurenines. Parkinson’s disease and other neurodegenerative disorders: preclinical and clinical studies. J Neural Transm Suppl 70:285–304

    Article  PubMed  CAS  Google Scholar 

  • Nemeth H, Robotka H, Toldi J, Vecsei L (2007) Kynurenines in the central nervous system: recent developments. Cent Nerv Syst Agents Med Chem 7:45–46

    Article  CAS  Google Scholar 

  • Prescott C, Weeks AM, Staley KJ, Partin KM (2006) Kynurenic acid has a dual action on AMPA receptor responses. Neurosci Lett 402:108–112

    Article  PubMed  CAS  Google Scholar 

  • Rajda C, Bergquist J, Vecsei L (2007) Kynurenines, redox disturbances and neurodegeneration in multiple sclerosis. J Neural Transm Suppl 72:323–329

    Article  PubMed  CAS  Google Scholar 

  • Robotka H, Toldi J, Vecsei L (2008) L-Kynurenine: metabolism and mechanism of neuroprotection. Future Neurol 3:169–188

    Article  CAS  Google Scholar 

  • Rozsa E, Robotka H, Vecsei L, Toldi J (2008) The Janus-face kynurenic acid. J Neural Transm 115:1087–1091

    Article  PubMed  CAS  Google Scholar 

  • Sas K, Robotka H, Toldi J, Vecsei L (2007) Mitochondria, metabolic disturbances, oxidative stress and the kynurenine system, with focus on neurodegenerative disorders. J Neurol Sci 257:221–239

    Article  PubMed  CAS  Google Scholar 

  • Scharfman HE, Goodman JH (1998) Effects of central and peripheral administration of kynurenic acid on hippocampal evoked responses in vivo and in vitro. Neurosci 86:751–764

    Google Scholar 

  • Stone TW (2001) Kynurenic acid antagonists and kynurenine pathway inhibitors. Expert Opin Investig Drugs 10:633–645

    Article  PubMed  CAS  Google Scholar 

  • Turski MP, Turska M, Zgrajka W, Kuc D, Turski WA (2009) Presence of kynurenic acid in food and honeybee products. Amino Acids 36:75–80

    Article  PubMed  CAS  Google Scholar 

  • Turski MP, Turska M, Zgrajka W, Bartnik M, Kocki T, Turski WA (2011) Distribution. Synthesis, and Absorption of Kynurenic Acid in Plants. Planta Med 77:858–864

    CAS  Google Scholar 

  • Wolf H (1974) Studies on tryptophan metabolism in man. Scan J Clin Lab Invest 136S:1–186

    Google Scholar 

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Acknowledgments

The present study was supported by TÁMOP-4.2.1/B-09/1/KONV-2010-005 and OTKA K 75628.

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Authors and Affiliations

  1. Institute of Pharmaceutical Chemistry and Research Group for Stereochemistry, Hungarian Academy of Sciences, University of Szeged, Eotvos u. 6, 6720, Szeged, Hungary

    Ferenc Fülöp & István Szatmári

  2. Department of Physiology, Anatomy and Neuroscience, University of Szeged, Közép fasor 52, 6726, Szeged, Hungary

    József Toldi

  3. Department of Neurology, University of Szeged, P. O. Box 427, 6701, Szeged, Hungary

    László Vécsei

Authors
  1. Ferenc Fülöp
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  2. István Szatmári
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  3. József Toldi
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  4. László Vécsei
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Correspondence to Ferenc Fülöp.

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Fülöp, F., Szatmári, I., Toldi, J. et al. Modifications on the carboxylic function of kynurenic acid. J Neural Transm 119, 109–114 (2012). https://doi.org/10.1007/s00702-011-0721-7

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  • DOI: https://doi.org/10.1007/s00702-011-0721-7

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