A Prodrug Form of a Plasmodium falciparum Glutathione Reductase Inhibitor Conjugated with a 4-Anilinoquinoline
Identifieur interne : 002289 ( Main/Exploration ); précédent : 002288; suivant : 002290A Prodrug Form of a Plasmodium falciparum Glutathione Reductase Inhibitor Conjugated with a 4-Anilinoquinoline
Auteurs : Elisabeth Davioud-Charvet [Allemagne, États-Unis] ; Sandrine Delarue [Allemagne] ; Christophe Biot [Allemagne] ; Babett Schwöbel [Allemagne] ; Catharina C. Boehme [Allemagne] ; Andreas Müssigbrodt [Allemagne] ; Louis Maes [Allemagne] ; Christian Sergheraert [Allemagne] ; Philippe Grellier [Allemagne] ; R. Heiner Schirmer [Allemagne] ; Katja Becker [Allemagne]Source :
- Journal of Medicinal Chemistry [ 0022-2623 ] ; 2001.
Abstract
Glutathione (GSH), which is known to guard Plasmodium falciparum from oxidative damage, may have an additional protective role by promoting heme catabolism. An elevation of GSH content in parasites leads to increased resistance to chloroquine (CQ), while GSH depletion in resistant P. falciparum strains is expected to restore the sensitivity to CQ. High intracellular GSH levels depend inter alia on the efficient reduction of GSSG by glutathione reductase (GR). On the basis of this hypothesis, we have developed a new strategy for overcoming glutathione-dependent 4-aminoquinoline resistance. To direct both a 4-aminoquinoline and a GR inhibitor to the parasite, double-drugs were designed and synthesized. Quinoline-based alcohols (with known antimalarial activity) were combined with a GR inhibitor via a metabolically labile ester bond to give double-headed prodrugs. The biochemically most active double-drug 7 of this series was then evaluated as a growth inhibitor against six Plasmodium falciparum strains that differed in their degree of resistance to CQ; the ED50 values for CQ ranged from 14 to 183 nM. While the inhibitory activity of the original 4-aminoquinoline-based alcohol followed that of CQ in these tests, the double-drug exhibited similar efficiency against all strains, the ED50 being as low as 28 nM. For the ester 7, a dose-dependent decrease in glutathione content and GR activity and an increase in glutathione-S-transferase activity were determined in treated parasites. The drug was subsequently tested for its antimalarial action in vivo using murine malaria models infected with P. berghei. A 178% excess mean survival time was determined for the animals treated with 40 mg/kg 7 for 4 days. No cytotoxicity due to this compound was observed. Work is in progress to extend and validate the strategy outlined here.
Url:
DOI: 10.1021/jm010268g
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream Istex, to step Corpus: 000194
- to stream Istex, to step Curation: 000194
- to stream Istex, to step Checkpoint: 001113
- to stream Main, to step Merge: 002313
- to stream Main, to step Curation: 002289
Le document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title>A Prodrug Form of a Plasmodium falciparum Glutathione Reductase Inhibitor Conjugated with a 4-Anilinoquinoline</title><author><name sortKey="Davioud Charvet, Elisabeth" sort="Davioud Charvet, Elisabeth" uniqKey="Davioud Charvet E" first="Elisabeth" last="Davioud-Charvet">Elisabeth Davioud-Charvet</name></author><author><name sortKey="Delarue, Sandrine" sort="Delarue, Sandrine" uniqKey="Delarue S" first="Sandrine" last="Delarue">Sandrine Delarue</name></author><author><name sortKey="Biot, Christophe" sort="Biot, Christophe" uniqKey="Biot C" first="Christophe" last="Biot">Christophe Biot</name></author><author><name sortKey="Schwobel, Babett" sort="Schwobel, Babett" uniqKey="Schwobel B" first="Babett" last="Schwöbel">Babett Schwöbel</name></author><author><name sortKey="Boehme, Catharina C" sort="Boehme, Catharina C" uniqKey="Boehme C" first="Catharina C." last="Boehme">Catharina C. Boehme</name></author><author><name sortKey="Mussigbrodt, Andreas" sort="Mussigbrodt, Andreas" uniqKey="Mussigbrodt A" first="Andreas" last="Müssigbrodt">Andreas Müssigbrodt</name></author><author><name sortKey="Maes, Louis" sort="Maes, Louis" uniqKey="Maes L" first="Louis" last="Maes">Louis Maes</name></author><author><name sortKey="Sergheraert, Christian" sort="Sergheraert, Christian" uniqKey="Sergheraert C" first="Christian" last="Sergheraert">Christian Sergheraert</name></author><author><name sortKey="Grellier, Philippe" sort="Grellier, Philippe" uniqKey="Grellier P" first="Philippe" last="Grellier">Philippe Grellier</name></author><author><name sortKey="Schirmer, R Heiner" sort="Schirmer, R Heiner" uniqKey="Schirmer R" first="R. Heiner" last="Schirmer">R. Heiner Schirmer</name></author><author><name sortKey="Becker, Katja" sort="Becker, Katja" uniqKey="Becker K" first="Katja" last="Becker">Katja Becker</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:E43EEA0ED3C756078348A9AE186AEAF4B52291FC</idno><date when="2001" year="2001">2001</date><idno type="doi">10.1021/jm010268g</idno><idno type="url">https://api.istex.fr/ark:/67375/TPS-NQT42VGL-Q/fulltext.pdf</idno><idno type="wicri:Area/Istex/Corpus">000194</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">000194</idno><idno type="wicri:Area/Istex/Curation">000194</idno><idno type="wicri:Area/Istex/Checkpoint">001113</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Checkpoint">001113</idno><idno type="wicri:doubleKey">0022-2623:2001:Davioud Charvet E:a:prodrug:form</idno><idno type="wicri:Area/Main/Merge">002313</idno><idno type="wicri:Area/Main/Curation">002289</idno><idno type="wicri:Area/Main/Exploration">002289</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">A Prodrug Form of a <hi rend="italic">Plasmodium falciparum </hi>Glutathione Reductase Inhibitor
Conjugated with a 4-Anilinoquinoline</title><author><name sortKey="Davioud Charvet, Elisabeth" sort="Davioud Charvet, Elisabeth" uniqKey="Davioud Charvet E" first="Elisabeth" last="Davioud-Charvet">Elisabeth Davioud-Charvet</name><affiliation wicri:level="1"><country xml:lang="fr">Allemagne</country><wicri:regionArea>UMR 8525 CNRS−Université Lille II−Institut Pasteur de Lille, Institut de Biologie de Lille, 1 rue du Professeur Calmette,BP447 59021 Lille Cedex, France, Tibotec, L11 Gen. de Wittelaan, B-32800 Mechelen, Belgium, Laboratoire de BiologieParasitaire, Muséum National d'Histoire Naturelle, IFR CNRS 63, 61 rue Buffon, 75005 Paris, France, Biochemie-Zentrumder Universität Heidelberg, Im Neuenheimer Feld 328, D-69120 Heidelberg, Germany, and InterdisziplinäresForschungszentrum der Universität Giessen, Heinrich Buff-Ring 26-32, D-35392 Giessen</wicri:regionArea><wicri:noRegion>35392 Giessen</wicri:noRegion><wicri:noRegion>D-35392 Giessen</wicri:noRegion></affiliation><affiliation></affiliation><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Michigan</region></placeName><wicri:cityArea> Present address: College of Pharmacy, University of Michigan,428 Church Street, Ann Arbor</wicri:cityArea></affiliation><affiliation></affiliation></author><author><name sortKey="Delarue, Sandrine" sort="Delarue, Sandrine" uniqKey="Delarue S" first="Sandrine" last="Delarue">Sandrine Delarue</name><affiliation wicri:level="1"><country xml:lang="fr">Allemagne</country><wicri:regionArea>UMR 8525 CNRS−Université Lille II−Institut Pasteur de Lille, Institut de Biologie de Lille, 1 rue du Professeur Calmette,BP447 59021 Lille Cedex, France, Tibotec, L11 Gen. de Wittelaan, B-32800 Mechelen, Belgium, Laboratoire de BiologieParasitaire, Muséum National d'Histoire Naturelle, IFR CNRS 63, 61 rue Buffon, 75005 Paris, France, Biochemie-Zentrumder Universität Heidelberg, Im Neuenheimer Feld 328, D-69120 Heidelberg, Germany, and InterdisziplinäresForschungszentrum der Universität Giessen, Heinrich Buff-Ring 26-32, D-35392 Giessen</wicri:regionArea><wicri:noRegion>35392 Giessen</wicri:noRegion><wicri:noRegion>D-35392 Giessen</wicri:noRegion></affiliation><affiliation></affiliation></author><author><name sortKey="Biot, Christophe" sort="Biot, Christophe" uniqKey="Biot C" first="Christophe" last="Biot">Christophe Biot</name><affiliation wicri:level="1"><country xml:lang="fr">Allemagne</country><wicri:regionArea>UMR 8525 CNRS−Université Lille II−Institut Pasteur de Lille, Institut de Biologie de Lille, 1 rue du Professeur Calmette,BP447 59021 Lille Cedex, France, Tibotec, L11 Gen. de Wittelaan, B-32800 Mechelen, Belgium, Laboratoire de BiologieParasitaire, Muséum National d'Histoire Naturelle, IFR CNRS 63, 61 rue Buffon, 75005 Paris, France, Biochemie-Zentrumder Universität Heidelberg, Im Neuenheimer Feld 328, D-69120 Heidelberg, Germany, and InterdisziplinäresForschungszentrum der Universität Giessen, Heinrich Buff-Ring 26-32, D-35392 Giessen</wicri:regionArea><wicri:noRegion>35392 Giessen</wicri:noRegion><wicri:noRegion>D-35392 Giessen</wicri:noRegion></affiliation><affiliation></affiliation></author><author><name sortKey="Schwobel, Babett" sort="Schwobel, Babett" uniqKey="Schwobel B" first="Babett" last="Schwöbel">Babett Schwöbel</name><affiliation wicri:level="1"><country xml:lang="fr">Allemagne</country><wicri:regionArea>UMR 8525 CNRS−Université Lille II−Institut Pasteur de Lille, Institut de Biologie de Lille, 1 rue du Professeur Calmette,BP447 59021 Lille Cedex, France, Tibotec, L11 Gen. de Wittelaan, B-32800 Mechelen, Belgium, Laboratoire de BiologieParasitaire, Muséum National d'Histoire Naturelle, IFR CNRS 63, 61 rue Buffon, 75005 Paris, France, Biochemie-Zentrumder Universität Heidelberg, Im Neuenheimer Feld 328, D-69120 Heidelberg, Germany, and InterdisziplinäresForschungszentrum der Universität Giessen, Heinrich Buff-Ring 26-32, D-35392 Giessen</wicri:regionArea><wicri:noRegion>35392 Giessen</wicri:noRegion><wicri:noRegion>D-35392 Giessen</wicri:noRegion></affiliation><affiliation></affiliation></author><author><name sortKey="Boehme, Catharina C" sort="Boehme, Catharina C" uniqKey="Boehme C" first="Catharina C." last="Boehme">Catharina C. Boehme</name><affiliation wicri:level="1"><country xml:lang="fr">Allemagne</country><wicri:regionArea>UMR 8525 CNRS−Université Lille II−Institut Pasteur de Lille, Institut de Biologie de Lille, 1 rue du Professeur Calmette,BP447 59021 Lille Cedex, France, Tibotec, L11 Gen. de Wittelaan, B-32800 Mechelen, Belgium, Laboratoire de BiologieParasitaire, Muséum National d'Histoire Naturelle, IFR CNRS 63, 61 rue Buffon, 75005 Paris, France, Biochemie-Zentrumder Universität Heidelberg, Im Neuenheimer Feld 328, D-69120 Heidelberg, Germany, and InterdisziplinäresForschungszentrum der Universität Giessen, Heinrich Buff-Ring 26-32, D-35392 Giessen</wicri:regionArea><wicri:noRegion>35392 Giessen</wicri:noRegion><wicri:noRegion>D-35392 Giessen</wicri:noRegion></affiliation><affiliation></affiliation><affiliation></affiliation></author><author><name sortKey="Mussigbrodt, Andreas" sort="Mussigbrodt, Andreas" uniqKey="Mussigbrodt A" first="Andreas" last="Müssigbrodt">Andreas Müssigbrodt</name><affiliation wicri:level="1"><country xml:lang="fr">Allemagne</country><wicri:regionArea>UMR 8525 CNRS−Université Lille II−Institut Pasteur de Lille, Institut de Biologie de Lille, 1 rue du Professeur Calmette,BP447 59021 Lille Cedex, France, Tibotec, L11 Gen. de Wittelaan, B-32800 Mechelen, Belgium, Laboratoire de BiologieParasitaire, Muséum National d'Histoire Naturelle, IFR CNRS 63, 61 rue Buffon, 75005 Paris, France, Biochemie-Zentrumder Universität Heidelberg, Im Neuenheimer Feld 328, D-69120 Heidelberg, Germany, and InterdisziplinäresForschungszentrum der Universität Giessen, Heinrich Buff-Ring 26-32, D-35392 Giessen</wicri:regionArea><wicri:noRegion>35392 Giessen</wicri:noRegion><wicri:noRegion>D-35392 Giessen</wicri:noRegion></affiliation><affiliation></affiliation></author><author><name sortKey="Maes, Louis" sort="Maes, Louis" uniqKey="Maes L" first="Louis" last="Maes">Louis Maes</name><affiliation wicri:level="1"><country xml:lang="fr">Allemagne</country><wicri:regionArea>UMR 8525 CNRS−Université Lille II−Institut Pasteur de Lille, Institut de Biologie de Lille, 1 rue du Professeur Calmette,BP447 59021 Lille Cedex, France, Tibotec, L11 Gen. de Wittelaan, B-32800 Mechelen, Belgium, Laboratoire de BiologieParasitaire, Muséum National d'Histoire Naturelle, IFR CNRS 63, 61 rue Buffon, 75005 Paris, France, Biochemie-Zentrumder Universität Heidelberg, Im Neuenheimer Feld 328, D-69120 Heidelberg, Germany, and InterdisziplinäresForschungszentrum der Universität Giessen, Heinrich Buff-Ring 26-32, D-35392 Giessen</wicri:regionArea><wicri:noRegion>35392 Giessen</wicri:noRegion><wicri:noRegion>D-35392 Giessen</wicri:noRegion></affiliation><affiliation></affiliation></author><author><name sortKey="Sergheraert, Christian" sort="Sergheraert, Christian" uniqKey="Sergheraert C" first="Christian" last="Sergheraert">Christian Sergheraert</name><affiliation wicri:level="1"><country xml:lang="fr">Allemagne</country><wicri:regionArea>UMR 8525 CNRS−Université Lille II−Institut Pasteur de Lille, Institut de Biologie de Lille, 1 rue du Professeur Calmette,BP447 59021 Lille Cedex, France, Tibotec, L11 Gen. de Wittelaan, B-32800 Mechelen, Belgium, Laboratoire de BiologieParasitaire, Muséum National d'Histoire Naturelle, IFR CNRS 63, 61 rue Buffon, 75005 Paris, France, Biochemie-Zentrumder Universität Heidelberg, Im Neuenheimer Feld 328, D-69120 Heidelberg, Germany, and InterdisziplinäresForschungszentrum der Universität Giessen, Heinrich Buff-Ring 26-32, D-35392 Giessen</wicri:regionArea><wicri:noRegion>35392 Giessen</wicri:noRegion><wicri:noRegion>D-35392 Giessen</wicri:noRegion></affiliation><affiliation></affiliation></author><author><name sortKey="Grellier, Philippe" sort="Grellier, Philippe" uniqKey="Grellier P" first="Philippe" last="Grellier">Philippe Grellier</name><affiliation wicri:level="1"><country xml:lang="fr">Allemagne</country><wicri:regionArea>UMR 8525 CNRS−Université Lille II−Institut Pasteur de Lille, Institut de Biologie de Lille, 1 rue du Professeur Calmette,BP447 59021 Lille Cedex, France, Tibotec, L11 Gen. de Wittelaan, B-32800 Mechelen, Belgium, Laboratoire de BiologieParasitaire, Muséum National d'Histoire Naturelle, IFR CNRS 63, 61 rue Buffon, 75005 Paris, France, Biochemie-Zentrumder Universität Heidelberg, Im Neuenheimer Feld 328, D-69120 Heidelberg, Germany, and InterdisziplinäresForschungszentrum der Universität Giessen, Heinrich Buff-Ring 26-32, D-35392 Giessen</wicri:regionArea><wicri:noRegion>35392 Giessen</wicri:noRegion><wicri:noRegion>D-35392 Giessen</wicri:noRegion></affiliation><affiliation></affiliation></author><author><name sortKey="Schirmer, R Heiner" sort="Schirmer, R Heiner" uniqKey="Schirmer R" first="R. Heiner" last="Schirmer">R. Heiner Schirmer</name><affiliation wicri:level="1"><country xml:lang="fr">Allemagne</country><wicri:regionArea>UMR 8525 CNRS−Université Lille II−Institut Pasteur de Lille, Institut de Biologie de Lille, 1 rue du Professeur Calmette,BP447 59021 Lille Cedex, France, Tibotec, L11 Gen. de Wittelaan, B-32800 Mechelen, Belgium, Laboratoire de BiologieParasitaire, Muséum National d'Histoire Naturelle, IFR CNRS 63, 61 rue Buffon, 75005 Paris, France, Biochemie-Zentrumder Universität Heidelberg, Im Neuenheimer Feld 328, D-69120 Heidelberg, Germany, and InterdisziplinäresForschungszentrum der Universität Giessen, Heinrich Buff-Ring 26-32, D-35392 Giessen</wicri:regionArea><wicri:noRegion>35392 Giessen</wicri:noRegion><wicri:noRegion>D-35392 Giessen</wicri:noRegion></affiliation><affiliation></affiliation></author><author><name sortKey="Becker, Katja" sort="Becker, Katja" uniqKey="Becker K" first="Katja" last="Becker">Katja Becker</name><affiliation wicri:level="1"><country xml:lang="fr">Allemagne</country><wicri:regionArea>UMR 8525 CNRS−Université Lille II−Institut Pasteur de Lille, Institut de Biologie de Lille, 1 rue du Professeur Calmette,BP447 59021 Lille Cedex, France, Tibotec, L11 Gen. de Wittelaan, B-32800 Mechelen, Belgium, Laboratoire de BiologieParasitaire, Muséum National d'Histoire Naturelle, IFR CNRS 63, 61 rue Buffon, 75005 Paris, France, Biochemie-Zentrumder Universität Heidelberg, Im Neuenheimer Feld 328, D-69120 Heidelberg, Germany, and InterdisziplinäresForschungszentrum der Universität Giessen, Heinrich Buff-Ring 26-32, D-35392 Giessen</wicri:regionArea><wicri:noRegion>35392 Giessen</wicri:noRegion><wicri:noRegion>D-35392 Giessen</wicri:noRegion></affiliation><affiliation></affiliation><affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">Journal of Medicinal Chemistry</title><title level="j" type="abbrev">J. Med. Chem.</title><idno type="ISSN">0022-2623</idno><idno type="eISSN">1520-4804</idno><imprint><publisher>American Chemical Society</publisher><date type="e-published" when="2001-10-26">2001</date><date when="2001-11-22">2001</date><biblScope unit="vol">44</biblScope><biblScope unit="issue">24</biblScope><biblScope unit="page" from="4268">4268</biblScope><biblScope unit="page" to="4276">4276</biblScope></imprint><idno type="ISSN">0022-2623</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0022-2623</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract">Glutathione (GSH), which is known to guard Plasmodium falciparum from oxidative damage, may have an additional protective role by promoting heme catabolism. An elevation of GSH content in parasites leads to increased resistance to chloroquine (CQ), while GSH depletion in resistant P. falciparum strains is expected to restore the sensitivity to CQ. High intracellular GSH levels depend inter alia on the efficient reduction of GSSG by glutathione reductase (GR). On the basis of this hypothesis, we have developed a new strategy for overcoming glutathione-dependent 4-aminoquinoline resistance. To direct both a 4-aminoquinoline and a GR inhibitor to the parasite, double-drugs were designed and synthesized. Quinoline-based alcohols (with known antimalarial activity) were combined with a GR inhibitor via a metabolically labile ester bond to give double-headed prodrugs. The biochemically most active double-drug 7 of this series was then evaluated as a growth inhibitor against six Plasmodium falciparum strains that differed in their degree of resistance to CQ; the ED50 values for CQ ranged from 14 to 183 nM. While the inhibitory activity of the original 4-aminoquinoline-based alcohol followed that of CQ in these tests, the double-drug exhibited similar efficiency against all strains, the ED50 being as low as 28 nM. For the ester 7, a dose-dependent decrease in glutathione content and GR activity and an increase in glutathione-S-transferase activity were determined in treated parasites. The drug was subsequently tested for its antimalarial action in vivo using murine malaria models infected with P. berghei. A 178% excess mean survival time was determined for the animals treated with 40 mg/kg 7 for 4 days. No cytotoxicity due to this compound was observed. Work is in progress to extend and validate the strategy outlined here.</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>États-Unis</li></country><region><li>Michigan</li></region></list><tree><country name="Allemagne"><noRegion><name sortKey="Davioud Charvet, Elisabeth" sort="Davioud Charvet, Elisabeth" uniqKey="Davioud Charvet E" first="Elisabeth" last="Davioud-Charvet">Elisabeth Davioud-Charvet</name></noRegion><name sortKey="Becker, Katja" sort="Becker, Katja" uniqKey="Becker K" first="Katja" last="Becker">Katja Becker</name><name sortKey="Biot, Christophe" sort="Biot, Christophe" uniqKey="Biot C" first="Christophe" last="Biot">Christophe Biot</name><name sortKey="Boehme, Catharina C" sort="Boehme, Catharina C" uniqKey="Boehme C" first="Catharina C." last="Boehme">Catharina C. Boehme</name><name sortKey="Delarue, Sandrine" sort="Delarue, Sandrine" uniqKey="Delarue S" first="Sandrine" last="Delarue">Sandrine Delarue</name><name sortKey="Grellier, Philippe" sort="Grellier, Philippe" uniqKey="Grellier P" first="Philippe" last="Grellier">Philippe Grellier</name><name sortKey="Maes, Louis" sort="Maes, Louis" uniqKey="Maes L" first="Louis" last="Maes">Louis Maes</name><name sortKey="Mussigbrodt, Andreas" sort="Mussigbrodt, Andreas" uniqKey="Mussigbrodt A" first="Andreas" last="Müssigbrodt">Andreas Müssigbrodt</name><name sortKey="Schirmer, R Heiner" sort="Schirmer, R Heiner" uniqKey="Schirmer R" first="R. Heiner" last="Schirmer">R. Heiner Schirmer</name><name sortKey="Schwobel, Babett" sort="Schwobel, Babett" uniqKey="Schwobel B" first="Babett" last="Schwöbel">Babett Schwöbel</name><name sortKey="Sergheraert, Christian" sort="Sergheraert, Christian" uniqKey="Sergheraert C" first="Christian" last="Sergheraert">Christian Sergheraert</name></country><country name="États-Unis"><region name="Michigan"><name sortKey="Davioud Charvet, Elisabeth" sort="Davioud Charvet, Elisabeth" uniqKey="Davioud Charvet E" first="Elisabeth" last="Davioud-Charvet">Elisabeth Davioud-Charvet</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/ChloroquineV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 002289 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 002289 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= ChloroquineV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= ISTEX:E43EEA0ED3C756078348A9AE186AEAF4B52291FC
|texte= A Prodrug Form of a Plasmodium falciparum Glutathione Reductase Inhibitor Conjugated with a 4-Anilinoquinoline
}}
| This area was generated with Dilib version V0.6.33. |  |