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01-02-2012 | Basic Neurosciences, Genetics and Immunology - Original Article

Modifications on the carboxylic function of kynurenic acid

Authors: Ferenc Fülöp, István Szatmári, József Toldi, László Vécsei

Published in: Journal of Neural Transmission | Issue 2/2012

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.

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 17:406–409PubMedCrossRef

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

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 16:4828–4842PubMedCrossRef

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 667:182–187PubMedCrossRef

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 564:116–122PubMedCrossRef

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 300:719–724PubMedCrossRef

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 21:7463–7473PubMed

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

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 55:443–447PubMed

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

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 2:249–260PubMedCrossRef

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

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

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

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

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

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

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 257:221–239PubMedCrossRef

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

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

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

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

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

Title: Modifications on the carboxylic function of kynurenic acid
Authors: Ferenc Fülöp
István Szatmári
József Toldi
László Vécsei
Publication date: 01-02-2012
Publisher: Springer Vienna
Published in: Journal of Neural Transmission / Issue 2/2012
Print ISSN: 0300-9564
Electronic ISSN: 1435-1463
DOI: https://doi.org/10.1007/s00702-011-0721-7

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Modifications on the carboxylic function of kynurenic acid

Abstract

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Springer Medicine

Abstract

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