Neuroprotective effects of a brain permeant 6-aminoquinoxaline derivative in cell culture conditions that model the loss of dopaminergic neurons in Parkinson disease.
Identifieur interne : 000412 ( PubMed/Corpus ); précédent : 000411; suivant : 000413Neuroprotective effects of a brain permeant 6-aminoquinoxaline derivative in cell culture conditions that model the loss of dopaminergic neurons in Parkinson disease.
Auteurs : Gael Le Douaron ; Fanny Schmidt ; Majid Amar ; Hanane Kadar ; Lucila Debortoli ; Alexandra Latini ; Blandine Séon-Méniel ; Laurent Ferrié ; Patrick Pierre Michel ; David Touboul ; Alain Brunelle ; Rita Raisman-Vozari ; Bruno FigadèreSource :
- European journal of medicinal chemistry [ 1768-3254 ] ; 2015.
English descriptors
- KwdEn :
- Animals, Brain (drug effects), Brain (pathology), Cell Culture Techniques, Cells, Cultured, Dopaminergic Neurons (drug effects), Dopaminergic Neurons (pathology), Male, Mice, Inbred C57BL, Molecular Structure, Neuroprotective Agents (chemical synthesis), Neuroprotective Agents (chemistry), Neuroprotective Agents (pharmacokinetics), Neuroprotective Agents (pharmacology), Parkinson Disease (pathology), Quantitative Structure-Activity Relationship, Quinoxalines (chemical synthesis), Quinoxalines (chemistry), Quinoxalines (pharmacokinetics), Quinoxalines (pharmacology), Rats, Sprague-Dawley, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Tissue Distribution.
- MESH :
- chemical , chemical synthesis : Neuroprotective Agents, Quinoxalines.
- chemical , chemistry : Neuroprotective Agents, Quinoxalines.
- drug effects : Brain, Dopaminergic Neurons.
- pathology : Brain, Dopaminergic Neurons, Parkinson Disease.
- chemical , pharmacokinetics : Neuroprotective Agents, Quinoxalines.
- chemical , pharmacology : Neuroprotective Agents, Quinoxalines.
- Animals, Cell Culture Techniques, Cells, Cultured, Male, Mice, Inbred C57BL, Molecular Structure, Quantitative Structure-Activity Relationship, Rats, Sprague-Dawley, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Tissue Distribution.
Abstract
Parkinson disease is a neurodegenerative disorder of aging, characterized by disabling motor symptoms resulting from the loss of midbrain dopaminergic neurons and the decrease of dopamine in the striatum. Current therapies are directed at treating the symptoms but there is presently no cure for the disease. In order to discover neuroprotective compounds with a therapeutical potential, our research team has established original and highly regioselective methods for the synthesis of 2,3-disubstituted 6-aminoquinoxalines. To evaluate the neuroprotective activity of these molecules, we used midbrain cultures and various experimental conditions that promote dopaminergic cell loss. Among a series of 11 molecules, only compound MPAQ (2-methyl-3-phenyl-6-aminoquinoxaline) afforded substantial protection in a paradigm where dopaminergic neurons die spontaneously and progressively as they mature. Prediction of blood-brain barrier permeation by Quantitative Structure-Activity Relationship studies (QSARs) suggested that MPAQ was able to reach the brain parenchyma with sufficient efficacy. HPLC-MS/MS quantification in brain homogenates and MALDI-TOF mass spectrometry imaging on brain tissue sections performed in MPAQ-treated mice allowed us to confirm this prediction and to demonstrate, by MALDI-TOF mass spectrometry imaging, that MPAQ was localized in areas containing vulnerable neurons and/or their terminals. Of interest, MPAQ also rescued dopaminergic neurons, which (i) acquired dependency on the trophic peptide GDNF for their survival or (ii) underwent oxidative stress-mediated insults mediated by catalytically active iron. In summary, MPAQ possesses an interesting pharmacological profile as it penetrates the brain parenchyma and counteracts mechanisms possibly contributive to dopaminergic cell death in Parkinson disease.
DOI: 10.1016/j.ejmech.2014.10.067
PubMed: 25462259
Links to Exploration step
pubmed:25462259Le document en format XML
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Sorbonne Université Pierre et Marie Curie-Paris UM75, INSERM U1127, CNRS UMR7225, Institut du Cerveau et de la Moelle Epinière, Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Amar, Majid" sort="Amar, Majid" uniqKey="Amar M" first="Majid" last="Amar">Majid Amar</name><affiliation><nlm:affiliation>Centre Nationale de la Recherche Scientifique (CNRS), Unité mixte de recherche (UMR) 8076 BioCIS, LabEx LERMIT, Laboratoire de Pharmacognosie, Université Paris-Sud, Faculté de Pharmacie, Châtenay-Malabry, France; Sorbonne Université Pierre et Marie Curie-Paris UM75, INSERM U1127, CNRS UMR7225, Institut du Cerveau et de la Moelle Epinière, Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Kadar, Hanane" sort="Kadar, Hanane" uniqKey="Kadar H" first="Hanane" last="Kadar">Hanane Kadar</name><affiliation><nlm:affiliation>Institut de Chimie des Substances Naturelles, CNRS, Gif-sur-Yvette Cedex, France.</nlm:affiliation></affiliation></author><author><name sortKey="Debortoli, Lucila" sort="Debortoli, Lucila" uniqKey="Debortoli L" first="Lucila" last="Debortoli">Lucila Debortoli</name><affiliation><nlm:affiliation>Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade Florianópolis, Brazil.</nlm:affiliation></affiliation></author><author><name sortKey="Latini, Alexandra" sort="Latini, Alexandra" uniqKey="Latini A" first="Alexandra" last="Latini">Alexandra Latini</name><affiliation><nlm:affiliation>Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade Florianópolis, Brazil.</nlm:affiliation></affiliation></author><author><name sortKey="Seon Meniel, Blandine" sort="Seon Meniel, Blandine" uniqKey="Seon Meniel B" first="Blandine" last="Séon-Méniel">Blandine Séon-Méniel</name><affiliation><nlm:affiliation>Centre Nationale de la Recherche Scientifique (CNRS), Unité mixte de recherche (UMR) 8076 BioCIS, LabEx LERMIT, Laboratoire de Pharmacognosie, Université Paris-Sud, Faculté de Pharmacie, Châtenay-Malabry, France.</nlm:affiliation></affiliation></author><author><name sortKey="Ferrie, Laurent" sort="Ferrie, Laurent" uniqKey="Ferrie L" first="Laurent" last="Ferrié">Laurent Ferrié</name><affiliation><nlm:affiliation>Centre Nationale de la Recherche Scientifique (CNRS), Unité mixte de recherche (UMR) 8076 BioCIS, LabEx LERMIT, Laboratoire de Pharmacognosie, Université Paris-Sud, Faculté de Pharmacie, Châtenay-Malabry, France.</nlm:affiliation></affiliation></author><author><name sortKey="Michel, Patrick Pierre" sort="Michel, Patrick Pierre" uniqKey="Michel P" first="Patrick Pierre" last="Michel">Patrick Pierre Michel</name><affiliation><nlm:affiliation>Sorbonne Université Pierre et Marie Curie-Paris UM75, INSERM U1127, CNRS UMR7225, Institut du Cerveau et de la Moelle Epinière, Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Touboul, David" sort="Touboul, David" uniqKey="Touboul D" first="David" last="Touboul">David Touboul</name><affiliation><nlm:affiliation>Institut de Chimie des Substances Naturelles, CNRS, Gif-sur-Yvette Cedex, France.</nlm:affiliation></affiliation></author><author><name sortKey="Brunelle, Alain" sort="Brunelle, Alain" uniqKey="Brunelle A" first="Alain" last="Brunelle">Alain Brunelle</name><affiliation><nlm:affiliation>Institut de Chimie des Substances Naturelles, CNRS, Gif-sur-Yvette Cedex, France.</nlm:affiliation></affiliation></author><author><name sortKey="Raisman Vozari, Rita" sort="Raisman Vozari, Rita" uniqKey="Raisman Vozari R" first="Rita" last="Raisman-Vozari">Rita Raisman-Vozari</name><affiliation><nlm:affiliation>Sorbonne Université Pierre et Marie Curie-Paris UM75, INSERM U1127, CNRS UMR7225, Institut du Cerveau et de la Moelle Epinière, Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Figadere, Bruno" sort="Figadere, Bruno" uniqKey="Figadere B" first="Bruno" last="Figadère">Bruno Figadère</name><affiliation><nlm:affiliation>Centre Nationale de la Recherche Scientifique (CNRS), Unité mixte de recherche (UMR) 8076 BioCIS, LabEx LERMIT, Laboratoire de Pharmacognosie, Université Paris-Sud, Faculté de Pharmacie, Châtenay-Malabry, France. Electronic address: bruno.figadere@u-psud.fr.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2015">2015</date><idno type="RBID">pubmed:25462259</idno><idno type="pmid">25462259</idno><idno type="doi">10.1016/j.ejmech.2014.10.067</idno><idno type="wicri:Area/PubMed/Corpus">000412</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000412</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Neuroprotective effects of a brain permeant 6-aminoquinoxaline derivative in cell culture conditions that model the loss of dopaminergic neurons in Parkinson disease.</title><author><name sortKey="Le Douaron, Gael" sort="Le Douaron, Gael" uniqKey="Le Douaron G" first="Gael" last="Le Douaron">Gael Le Douaron</name><affiliation><nlm:affiliation>Centre Nationale de la Recherche Scientifique (CNRS), Unité mixte de recherche (UMR) 8076 BioCIS, LabEx LERMIT, Laboratoire de Pharmacognosie, Université Paris-Sud, Faculté de Pharmacie, Châtenay-Malabry, France; Sorbonne Université Pierre et Marie Curie-Paris UM75, INSERM U1127, CNRS UMR7225, Institut du Cerveau et de la Moelle Epinière, Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Schmidt, Fanny" sort="Schmidt, Fanny" uniqKey="Schmidt F" first="Fanny" last="Schmidt">Fanny Schmidt</name><affiliation><nlm:affiliation>Centre Nationale de la Recherche Scientifique (CNRS), Unité mixte de recherche (UMR) 8076 BioCIS, LabEx LERMIT, Laboratoire de Pharmacognosie, Université Paris-Sud, Faculté de Pharmacie, Châtenay-Malabry, France; Sorbonne Université Pierre et Marie Curie-Paris UM75, INSERM U1127, CNRS UMR7225, Institut du Cerveau et de la Moelle Epinière, Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Amar, Majid" sort="Amar, Majid" uniqKey="Amar M" first="Majid" last="Amar">Majid Amar</name><affiliation><nlm:affiliation>Centre Nationale de la Recherche Scientifique (CNRS), Unité mixte de recherche (UMR) 8076 BioCIS, LabEx LERMIT, Laboratoire de Pharmacognosie, Université Paris-Sud, Faculté de Pharmacie, Châtenay-Malabry, France; Sorbonne Université Pierre et Marie Curie-Paris UM75, INSERM U1127, CNRS UMR7225, Institut du Cerveau et de la Moelle Epinière, Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Kadar, Hanane" sort="Kadar, Hanane" uniqKey="Kadar H" first="Hanane" last="Kadar">Hanane Kadar</name><affiliation><nlm:affiliation>Institut de Chimie des Substances Naturelles, CNRS, Gif-sur-Yvette Cedex, France.</nlm:affiliation></affiliation></author><author><name sortKey="Debortoli, Lucila" sort="Debortoli, Lucila" uniqKey="Debortoli L" first="Lucila" last="Debortoli">Lucila Debortoli</name><affiliation><nlm:affiliation>Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade Florianópolis, Brazil.</nlm:affiliation></affiliation></author><author><name sortKey="Latini, Alexandra" sort="Latini, Alexandra" uniqKey="Latini A" first="Alexandra" last="Latini">Alexandra Latini</name><affiliation><nlm:affiliation>Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade Florianópolis, Brazil.</nlm:affiliation></affiliation></author><author><name sortKey="Seon Meniel, Blandine" sort="Seon Meniel, Blandine" uniqKey="Seon Meniel B" first="Blandine" last="Séon-Méniel">Blandine Séon-Méniel</name><affiliation><nlm:affiliation>Centre Nationale de la Recherche Scientifique (CNRS), Unité mixte de recherche (UMR) 8076 BioCIS, LabEx LERMIT, Laboratoire de Pharmacognosie, Université Paris-Sud, Faculté de Pharmacie, Châtenay-Malabry, France.</nlm:affiliation></affiliation></author><author><name sortKey="Ferrie, Laurent" sort="Ferrie, Laurent" uniqKey="Ferrie L" first="Laurent" last="Ferrié">Laurent Ferrié</name><affiliation><nlm:affiliation>Centre Nationale de la Recherche Scientifique (CNRS), Unité mixte de recherche (UMR) 8076 BioCIS, LabEx LERMIT, Laboratoire de Pharmacognosie, Université Paris-Sud, Faculté de Pharmacie, Châtenay-Malabry, France.</nlm:affiliation></affiliation></author><author><name sortKey="Michel, Patrick Pierre" sort="Michel, Patrick Pierre" uniqKey="Michel P" first="Patrick Pierre" last="Michel">Patrick Pierre Michel</name><affiliation><nlm:affiliation>Sorbonne Université Pierre et Marie Curie-Paris UM75, INSERM U1127, CNRS UMR7225, Institut du Cerveau et de la Moelle Epinière, Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Touboul, David" sort="Touboul, David" uniqKey="Touboul D" first="David" last="Touboul">David Touboul</name><affiliation><nlm:affiliation>Institut de Chimie des Substances Naturelles, CNRS, Gif-sur-Yvette Cedex, France.</nlm:affiliation></affiliation></author><author><name sortKey="Brunelle, Alain" sort="Brunelle, Alain" uniqKey="Brunelle A" first="Alain" last="Brunelle">Alain Brunelle</name><affiliation><nlm:affiliation>Institut de Chimie des Substances Naturelles, CNRS, Gif-sur-Yvette Cedex, France.</nlm:affiliation></affiliation></author><author><name sortKey="Raisman Vozari, Rita" sort="Raisman Vozari, Rita" uniqKey="Raisman Vozari R" first="Rita" last="Raisman-Vozari">Rita Raisman-Vozari</name><affiliation><nlm:affiliation>Sorbonne Université Pierre et Marie Curie-Paris UM75, INSERM U1127, CNRS UMR7225, Institut du Cerveau et de la Moelle Epinière, Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Figadere, Bruno" sort="Figadere, Bruno" uniqKey="Figadere B" first="Bruno" last="Figadère">Bruno Figadère</name><affiliation><nlm:affiliation>Centre Nationale de la Recherche Scientifique (CNRS), Unité mixte de recherche (UMR) 8076 BioCIS, LabEx LERMIT, Laboratoire de Pharmacognosie, Université Paris-Sud, Faculté de Pharmacie, Châtenay-Malabry, France. Electronic address: bruno.figadere@u-psud.fr.</nlm:affiliation></affiliation></author></analytic><series><title level="j">European journal of medicinal chemistry</title><idno type="eISSN">1768-3254</idno><imprint><date when="2015" type="published">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Brain (drug effects)</term><term>Brain (pathology)</term><term>Cell Culture Techniques</term><term>Cells, Cultured</term><term>Dopaminergic Neurons (drug effects)</term><term>Dopaminergic Neurons (pathology)</term><term>Male</term><term>Mice, Inbred C57BL</term><term>Molecular Structure</term><term>Neuroprotective Agents (chemical synthesis)</term><term>Neuroprotective Agents (chemistry)</term><term>Neuroprotective Agents (pharmacokinetics)</term><term>Neuroprotective Agents (pharmacology)</term><term>Parkinson Disease (pathology)</term><term>Quantitative Structure-Activity Relationship</term><term>Quinoxalines (chemical synthesis)</term><term>Quinoxalines (chemistry)</term><term>Quinoxalines (pharmacokinetics)</term><term>Quinoxalines (pharmacology)</term><term>Rats, Sprague-Dawley</term><term>Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization</term><term>Tissue Distribution</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemical synthesis" xml:lang="en"><term>Neuroprotective Agents</term><term>Quinoxalines</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Neuroprotective Agents</term><term>Quinoxalines</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Brain</term><term>Dopaminergic Neurons</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Brain</term><term>Dopaminergic Neurons</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacokinetics" xml:lang="en"><term>Neuroprotective Agents</term><term>Quinoxalines</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Neuroprotective Agents</term><term>Quinoxalines</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cell Culture Techniques</term><term>Cells, Cultured</term><term>Male</term><term>Mice, Inbred C57BL</term><term>Molecular Structure</term><term>Quantitative Structure-Activity Relationship</term><term>Rats, Sprague-Dawley</term><term>Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization</term><term>Tissue Distribution</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Parkinson disease is a neurodegenerative disorder of aging, characterized by disabling motor symptoms resulting from the loss of midbrain dopaminergic neurons and the decrease of dopamine in the striatum. Current therapies are directed at treating the symptoms but there is presently no cure for the disease. In order to discover neuroprotective compounds with a therapeutical potential, our research team has established original and highly regioselective methods for the synthesis of 2,3-disubstituted 6-aminoquinoxalines. To evaluate the neuroprotective activity of these molecules, we used midbrain cultures and various experimental conditions that promote dopaminergic cell loss. Among a series of 11 molecules, only compound MPAQ (2-methyl-3-phenyl-6-aminoquinoxaline) afforded substantial protection in a paradigm where dopaminergic neurons die spontaneously and progressively as they mature. Prediction of blood-brain barrier permeation by Quantitative Structure-Activity Relationship studies (QSARs) suggested that MPAQ was able to reach the brain parenchyma with sufficient efficacy. HPLC-MS/MS quantification in brain homogenates and MALDI-TOF mass spectrometry imaging on brain tissue sections performed in MPAQ-treated mice allowed us to confirm this prediction and to demonstrate, by MALDI-TOF mass spectrometry imaging, that MPAQ was localized in areas containing vulnerable neurons and/or their terminals. Of interest, MPAQ also rescued dopaminergic neurons, which (i) acquired dependency on the trophic peptide GDNF for their survival or (ii) underwent oxidative stress-mediated insults mediated by catalytically active iron. In summary, MPAQ possesses an interesting pharmacological profile as it penetrates the brain parenchyma and counteracts mechanisms possibly contributive to dopaminergic cell death in Parkinson disease.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">25462259</PMID><DateCreated><Year>2014</Year><Month>12</Month><Day>08</Day></DateCreated><DateCompleted><Year>2015</Year><Month>07</Month><Day>24</Day></DateCompleted><DateRevised><Year>2014</Year><Month>12</Month><Day>08</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1768-3254</ISSN><JournalIssue CitedMedium="Internet"><Volume>89</Volume><PubDate><Year>2015</Year><Month>Jan</Month><Day>07</Day></PubDate></JournalIssue><Title>European journal of medicinal chemistry</Title><ISOAbbreviation>Eur J Med Chem</ISOAbbreviation></Journal><ArticleTitle>Neuroprotective effects of a brain permeant 6-aminoquinoxaline derivative in cell culture conditions that model the loss of dopaminergic neurons in Parkinson disease.</ArticleTitle><Pagination><MedlinePgn>467-79</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.ejmech.2014.10.067</ELocationID><ELocationID EIdType="pii" ValidYN="Y">S0223-5234(14)00995-7</ELocationID><Abstract><AbstractText>Parkinson disease is a neurodegenerative disorder of aging, characterized by disabling motor symptoms resulting from the loss of midbrain dopaminergic neurons and the decrease of dopamine in the striatum. Current therapies are directed at treating the symptoms but there is presently no cure for the disease. In order to discover neuroprotective compounds with a therapeutical potential, our research team has established original and highly regioselective methods for the synthesis of 2,3-disubstituted 6-aminoquinoxalines. To evaluate the neuroprotective activity of these molecules, we used midbrain cultures and various experimental conditions that promote dopaminergic cell loss. Among a series of 11 molecules, only compound MPAQ (2-methyl-3-phenyl-6-aminoquinoxaline) afforded substantial protection in a paradigm where dopaminergic neurons die spontaneously and progressively as they mature. Prediction of blood-brain barrier permeation by Quantitative Structure-Activity Relationship studies (QSARs) suggested that MPAQ was able to reach the brain parenchyma with sufficient efficacy. HPLC-MS/MS quantification in brain homogenates and MALDI-TOF mass spectrometry imaging on brain tissue sections performed in MPAQ-treated mice allowed us to confirm this prediction and to demonstrate, by MALDI-TOF mass spectrometry imaging, that MPAQ was localized in areas containing vulnerable neurons and/or their terminals. Of interest, MPAQ also rescued dopaminergic neurons, which (i) acquired dependency on the trophic peptide GDNF for their survival or (ii) underwent oxidative stress-mediated insults mediated by catalytically active iron. In summary, MPAQ possesses an interesting pharmacological profile as it penetrates the brain parenchyma and counteracts mechanisms possibly contributive to dopaminergic cell death in Parkinson disease.</AbstractText><CopyrightInformation>Copyright © 2014 Elsevier Masson SAS. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Le Douaron</LastName><ForeName>Gael</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Centre Nationale de la Recherche Scientifique (CNRS), Unité mixte de recherche (UMR) 8076 BioCIS, LabEx LERMIT, Laboratoire de Pharmacognosie, Université Paris-Sud, Faculté de Pharmacie, Châtenay-Malabry, France; Sorbonne Université Pierre et Marie Curie-Paris UM75, INSERM U1127, CNRS UMR7225, Institut du Cerveau et de la Moelle Epinière, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Schmidt</LastName><ForeName>Fanny</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Centre Nationale de la Recherche Scientifique (CNRS), Unité mixte de recherche (UMR) 8076 BioCIS, LabEx LERMIT, Laboratoire de Pharmacognosie, Université Paris-Sud, Faculté de Pharmacie, Châtenay-Malabry, France; Sorbonne Université Pierre et Marie Curie-Paris UM75, INSERM U1127, CNRS UMR7225, Institut du Cerveau et de la Moelle Epinière, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Amar</LastName><ForeName>Majid</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Centre Nationale de la Recherche Scientifique (CNRS), Unité mixte de recherche (UMR) 8076 BioCIS, LabEx LERMIT, Laboratoire de Pharmacognosie, Université Paris-Sud, Faculté de Pharmacie, Châtenay-Malabry, France; Sorbonne Université Pierre et Marie Curie-Paris UM75, INSERM U1127, CNRS UMR7225, Institut du Cerveau et de la Moelle Epinière, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kadar</LastName><ForeName>Hanane</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Institut de Chimie des Substances Naturelles, CNRS, Gif-sur-Yvette Cedex, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Debortoli</LastName><ForeName>Lucila</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade Florianópolis, Brazil.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Latini</LastName><ForeName>Alexandra</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade Florianópolis, Brazil.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Séon-Méniel</LastName><ForeName>Blandine</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Centre Nationale de la Recherche Scientifique (CNRS), Unité mixte de recherche (UMR) 8076 BioCIS, LabEx LERMIT, Laboratoire de Pharmacognosie, Université Paris-Sud, Faculté de Pharmacie, Châtenay-Malabry, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ferrié</LastName><ForeName>Laurent</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Centre Nationale de la Recherche Scientifique (CNRS), Unité mixte de recherche (UMR) 8076 BioCIS, LabEx LERMIT, Laboratoire de Pharmacognosie, Université Paris-Sud, Faculté de Pharmacie, Châtenay-Malabry, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Michel</LastName><ForeName>Patrick Pierre</ForeName><Initials>PP</Initials><AffiliationInfo><Affiliation>Sorbonne Université Pierre et Marie Curie-Paris UM75, INSERM U1127, CNRS UMR7225, Institut du Cerveau et de la Moelle Epinière, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Touboul</LastName><ForeName>David</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Institut de Chimie des Substances Naturelles, CNRS, Gif-sur-Yvette Cedex, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Brunelle</LastName><ForeName>Alain</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Institut de Chimie des Substances Naturelles, CNRS, Gif-sur-Yvette Cedex, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Raisman-Vozari</LastName><ForeName>Rita</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Sorbonne Université Pierre et Marie Curie-Paris UM75, INSERM U1127, CNRS UMR7225, Institut du Cerveau et de la Moelle Epinière, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Figadère</LastName><ForeName>Bruno</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Centre Nationale de la Recherche Scientifique (CNRS), Unité mixte de recherche (UMR) 8076 BioCIS, LabEx LERMIT, Laboratoire de Pharmacognosie, Université Paris-Sud, Faculté de Pharmacie, Châtenay-Malabry, France. Electronic address: bruno.figadere@u-psud.fr.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2014</Year><Month>10</Month><Day>23</Day></ArticleDate></Article><MedlineJournalInfo><Country>France</Country><MedlineTA>Eur J Med Chem</MedlineTA><NlmUniqueID>0420510</NlmUniqueID><ISSNLinking>0223-5234</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D018696">Neuroprotective Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D011810">Quinoxalines</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001921" MajorTopicYN="N">Brain</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018929" MajorTopicYN="N">Cell Culture Techniques</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002478" MajorTopicYN="N">Cells, Cultured</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D059290" MajorTopicYN="N">Dopaminergic Neurons</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008810" MajorTopicYN="N">Mice, Inbred C57BL</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015394" MajorTopicYN="N">Molecular Structure</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018696" MajorTopicYN="N">Neuroprotective Agents</DescriptorName><QualifierName UI="Q000138" MajorTopicYN="Y">chemical synthesis</QualifierName><QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName><QualifierName UI="Q000493" MajorTopicYN="N">pharmacokinetics</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010300" MajorTopicYN="N">Parkinson Disease</DescriptorName><QualifierName UI="Q000473" MajorTopicYN="Y">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D021281" MajorTopicYN="N">Quantitative Structure-Activity Relationship</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011810" MajorTopicYN="N">Quinoxalines</DescriptorName><QualifierName UI="Q000138" MajorTopicYN="Y">chemical synthesis</QualifierName><QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName><QualifierName UI="Q000493" MajorTopicYN="N">pharmacokinetics</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D017207" MajorTopicYN="N">Rats, Sprague-Dawley</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D019032" MajorTopicYN="N">Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D014018" MajorTopicYN="N">Tissue Distribution</DescriptorName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Biological screening</Keyword><Keyword MajorTopicYN="N">MALDI-TOF imaging</Keyword><Keyword MajorTopicYN="N">Medicinal chemistry</Keyword><Keyword MajorTopicYN="N">Neurodegenerative disease</Keyword><Keyword MajorTopicYN="N">Parkinson disease</Keyword><Keyword MajorTopicYN="N">Quinoxaline</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2014</Year><Month>08</Month><Day>26</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2014</Year><Month>10</Month><Day>22</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2014</Year><Month>10</Month><Day>23</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2014</Year><Month>12</Month><Day>3</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2014</Year><Month>12</Month><Day>3</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2015</Year><Month>7</Month><Day>25</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">25462259</ArticleId><ArticleId IdType="pii">S0223-5234(14)00995-7</ArticleId><ArticleId IdType="doi">10.1016/j.ejmech.2014.10.067</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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