5-Substituted Tetrazoles as Bioisosteres of Carboxylic Acids. Bioisosterism and Mechanistic Studies on Glutathione Reductase Inhibitors as Antimalarials
Identifieur interne : 000A31 ( Istex/Curation ); précédent : 000A30; suivant : 000A325-Substituted Tetrazoles as Bioisosteres of Carboxylic Acids. Bioisosterism and Mechanistic Studies on Glutathione Reductase Inhibitors as Antimalarials
Auteurs : Christophe Biot [Allemagne, France] ; Holger Bauer [Allemagne] ; R. Heiner Schirmer [Allemagne] ; Elisabeth Davioud-Charvet [Allemagne, France]Source :
- Journal of Medicinal Chemistry [ 0022-2623 ] ; 2004.
Abstract
Plasmodium parasites are exposed to elevated fluxes of reactive oxygen species during intraerythrocytic life. The most important antioxidative systems are based on the glutathione reductases of the malarial parasite Plasmodium falciparum and the host erythrocyte. The development of menadione chemistry has led to the selection of the carboxylic acid 6-[2‘-(3‘-methyl)-1‘,4‘-naphthoquinolyl] hexanoic acid M5 asan inhibitor of the parasitic enzyme. As reported here, revisiting the mechanism of M5 action revealed an uncompetitive inhibition type with respect to both NADPH and glutathione disulfide. Masking the polarity of the acidic function of M5 by ester or amide bonds improved antiplasmodial activity. Bioisosteric replacement of the carboxylic function by tetrazole to increase bioavailability and to maintain comparable acidity led to improved antimalarial properties as well, but only with the cyanoethyl-protected tetrazoles. Using computed ab initio quantum methods, detailed analyses of the electronic profiles and the molecular properties evidenced the similarity of M5 and the bioisoteric tetrazole T4. The potential binding site of these molecules is discussed in light of the recently solved crystallographic structure of P. falciparum enzyme.
Url:
DOI: 10.1021/jm0497545
Links toward previous steps (curation, corpus...)
- to stream Istex, to step Corpus: Pour aller vers cette notice dans l'étape Curation :000A31
Links to Exploration step
ISTEX:C9C87D4357E24AFC2F532515535998AE3A5034F9Le document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title>5-Substituted Tetrazoles as Bioisosteres of Carboxylic Acids. Bioisosterism and Mechanistic Studies on Glutathione Reductase Inhibitors as Antimalarials</title><author><name sortKey="Biot, Christophe" sort="Biot, Christophe" uniqKey="Biot C" first="Christophe" last="Biot">Christophe Biot</name><affiliation wicri:level="1"><mods:affiliation>Bioinformatique Génomique et Structurale, CP 165/61, Université Libre de Bruxelles, 50 Av. F. D. Roosevelt,B-1050 Brussels, Belgium, UMR 8525 CNRS-Université Lille II-Institut Pasteur de Lille, Institut de Biologie de Lille,1 rue du Professor Calmette, BP447 59021 Lille Cedex, France, and Biochemie-Zentrum der Universität Heidelberg,Im Neuenheimer Feld 504, 69120 Heidelberg, Germany</mods:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Bioinformatique Génomique et Structurale, CP 165/61, Université Libre de Bruxelles, 50 Av. F. D. Roosevelt,B-1050 Brussels, Belgium, UMR 8525 CNRS-Université Lille II-Institut Pasteur de Lille, Institut de Biologie de Lille,1 rue du Professor Calmette, BP447 59021 Lille Cedex, France, and Biochemie-Zentrum der Universität Heidelberg,Im Neuenheimer Feld 504, 69120 Heidelberg</wicri:regionArea></affiliation><affiliation><mods:affiliation> Université Libre de Bruxelles.</mods:affiliation><wicri:noCountry code="no comma"> Université Libre de Bruxelles.</wicri:noCountry></affiliation><affiliation wicri:level="1"><mods:affiliation> To whom correspondence should be addressed. E.D.-C.: tel, +49-6221-54-4188; fax, +49-6221-54-5586; e-mail, elisabeth.davioud@gmx.de.C.B.: tel, (33) 03 20 43 48 93; fax, (33) 03 20 43 65 85; e-mail,christophe.biot@ensc-lille.fr.</mods:affiliation><country wicri:rule="url">France</country><wicri:regionArea> To whom correspondence should be addressed. E.D.-C.: tel, +49-6221-54-4188; fax, +49-6221-54-5586; e-mail, elisabeth.davioud@gmx.de.C.B.: tel, (33) 03 20 43 48 93; fax, (33) 03 20 43 65 85; e-mail</wicri:regionArea></affiliation></author><author><name sortKey="Bauer, Holger" sort="Bauer, Holger" uniqKey="Bauer H" first="Holger" last="Bauer">Holger Bauer</name><affiliation wicri:level="1"><mods:affiliation>Bioinformatique Génomique et Structurale, CP 165/61, Université Libre de Bruxelles, 50 Av. F. D. Roosevelt,B-1050 Brussels, Belgium, UMR 8525 CNRS-Université Lille II-Institut Pasteur de Lille, Institut de Biologie de Lille,1 rue du Professor Calmette, BP447 59021 Lille Cedex, France, and Biochemie-Zentrum der Universität Heidelberg,Im Neuenheimer Feld 504, 69120 Heidelberg, Germany</mods:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Bioinformatique Génomique et Structurale, CP 165/61, Université Libre de Bruxelles, 50 Av. F. D. Roosevelt,B-1050 Brussels, Belgium, UMR 8525 CNRS-Université Lille II-Institut Pasteur de Lille, Institut de Biologie de Lille,1 rue du Professor Calmette, BP447 59021 Lille Cedex, France, and Biochemie-Zentrum der Universität Heidelberg,Im Neuenheimer Feld 504, 69120 Heidelberg</wicri:regionArea></affiliation><affiliation><mods:affiliation> Institut de Biologie de Lille.</mods:affiliation><wicri:noCountry code="no comma"> Institut de Biologie de Lille.</wicri:noCountry></affiliation><affiliation wicri:level="1"><mods:affiliation> Delegate (E.D.-C.) and Fellow (H.B.) of Centre National de laRecherche Scientifique, France in the frame of a French−Germancooperation with the University of Heidelberg, Germany.</mods:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea> Delegate (E.D.-C.) and Fellow (H.B.) of Centre National de laRecherche Scientifique, France in the frame of a French−Germancooperation with the University of Heidelberg</wicri:regionArea></affiliation><affiliation><mods:affiliation> Biochemie-Zentrum der Universität Heidelberg.</mods:affiliation><wicri:noCountry code="no comma"> Biochemie-Zentrum der Universität Heidelberg.</wicri:noCountry></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"><mods:affiliation>Bioinformatique Génomique et Structurale, CP 165/61, Université Libre de Bruxelles, 50 Av. F. D. Roosevelt,B-1050 Brussels, Belgium, UMR 8525 CNRS-Université Lille II-Institut Pasteur de Lille, Institut de Biologie de Lille,1 rue du Professor Calmette, BP447 59021 Lille Cedex, France, and Biochemie-Zentrum der Universität Heidelberg,Im Neuenheimer Feld 504, 69120 Heidelberg, Germany</mods:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Bioinformatique Génomique et Structurale, CP 165/61, Université Libre de Bruxelles, 50 Av. F. D. Roosevelt,B-1050 Brussels, Belgium, UMR 8525 CNRS-Université Lille II-Institut Pasteur de Lille, Institut de Biologie de Lille,1 rue du Professor Calmette, BP447 59021 Lille Cedex, France, and Biochemie-Zentrum der Universität Heidelberg,Im Neuenheimer Feld 504, 69120 Heidelberg</wicri:regionArea></affiliation><affiliation><mods:affiliation> Biochemie-Zentrum der Universität Heidelberg.</mods:affiliation><wicri:noCountry code="no comma"> Biochemie-Zentrum der Universität Heidelberg.</wicri:noCountry></affiliation></author><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"><mods:affiliation>Bioinformatique Génomique et Structurale, CP 165/61, Université Libre de Bruxelles, 50 Av. F. D. Roosevelt,B-1050 Brussels, Belgium, UMR 8525 CNRS-Université Lille II-Institut Pasteur de Lille, Institut de Biologie de Lille,1 rue du Professor Calmette, BP447 59021 Lille Cedex, France, and Biochemie-Zentrum der Universität Heidelberg,Im Neuenheimer Feld 504, 69120 Heidelberg, Germany</mods:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Bioinformatique Génomique et Structurale, CP 165/61, Université Libre de Bruxelles, 50 Av. F. D. Roosevelt,B-1050 Brussels, Belgium, UMR 8525 CNRS-Université Lille II-Institut Pasteur de Lille, Institut de Biologie de Lille,1 rue du Professor Calmette, BP447 59021 Lille Cedex, France, and Biochemie-Zentrum der Universität Heidelberg,Im Neuenheimer Feld 504, 69120 Heidelberg</wicri:regionArea></affiliation><affiliation><mods:affiliation> Institut de Biologie de Lille.</mods:affiliation><wicri:noCountry code="no comma"> Institut de Biologie de Lille.</wicri:noCountry></affiliation><affiliation wicri:level="1"><mods:affiliation> Delegate (E.D.-C.) and Fellow (H.B.) of Centre National de laRecherche Scientifique, France in the frame of a French−Germancooperation with the University of Heidelberg, Germany.</mods:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea> Delegate (E.D.-C.) and Fellow (H.B.) of Centre National de laRecherche Scientifique, France in the frame of a French−Germancooperation with the University of Heidelberg</wicri:regionArea></affiliation><affiliation><mods:affiliation> Biochemie-Zentrum der Universität Heidelberg.</mods:affiliation><wicri:noCountry code="no comma"> Biochemie-Zentrum der Universität Heidelberg.</wicri:noCountry></affiliation><affiliation wicri:level="1"><mods:affiliation> To whom correspondence should be addressed. E.D.-C.: tel, +49-6221-54-4188; fax, +49-6221-54-5586; e-mail, elisabeth.davioud@gmx.de.C.B.: tel, (33) 03 20 43 48 93; fax, (33) 03 20 43 65 85; e-mail,christophe.biot@ensc-lille.fr.</mods:affiliation><country wicri:rule="url">France</country><wicri:regionArea> To whom correspondence should be addressed. E.D.-C.: tel, +49-6221-54-4188; fax, +49-6221-54-5586; e-mail, elisabeth.davioud@gmx.de.C.B.: tel, (33) 03 20 43 48 93; fax, (33) 03 20 43 65 85; e-mail</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:C9C87D4357E24AFC2F532515535998AE3A5034F9</idno><date when="2004" year="2004">2004</date><idno type="doi">10.1021/jm0497545</idno><idno type="url">https://api.istex.fr/ark:/67375/TPS-X9C19PQL-5/fulltext.pdf</idno><idno type="wicri:Area/Istex/Corpus">000A31</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">000A31</idno><idno type="wicri:Area/Istex/Curation">000A31</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">5-Substituted Tetrazoles as Bioisosteres of Carboxylic Acids. Bioisosterism and
Mechanistic Studies on Glutathione Reductase Inhibitors as Antimalarials</title><author><name sortKey="Biot, Christophe" sort="Biot, Christophe" uniqKey="Biot C" first="Christophe" last="Biot">Christophe Biot</name><affiliation wicri:level="1"><mods:affiliation>Bioinformatique Génomique et Structurale, CP 165/61, Université Libre de Bruxelles, 50 Av. F. D. Roosevelt,B-1050 Brussels, Belgium, UMR 8525 CNRS-Université Lille II-Institut Pasteur de Lille, Institut de Biologie de Lille,1 rue du Professor Calmette, BP447 59021 Lille Cedex, France, and Biochemie-Zentrum der Universität Heidelberg,Im Neuenheimer Feld 504, 69120 Heidelberg, Germany</mods:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Bioinformatique Génomique et Structurale, CP 165/61, Université Libre de Bruxelles, 50 Av. F. D. Roosevelt,B-1050 Brussels, Belgium, UMR 8525 CNRS-Université Lille II-Institut Pasteur de Lille, Institut de Biologie de Lille,1 rue du Professor Calmette, BP447 59021 Lille Cedex, France, and Biochemie-Zentrum der Universität Heidelberg,Im Neuenheimer Feld 504, 69120 Heidelberg</wicri:regionArea></affiliation><affiliation><mods:affiliation> Université Libre de Bruxelles.</mods:affiliation></affiliation><affiliation wicri:level="1"><mods:affiliation> To whom correspondence should be addressed. E.D.-C.: tel, +49-6221-54-4188; fax, +49-6221-54-5586; e-mail, elisabeth.davioud@gmx.de.C.B.: tel, (33) 03 20 43 48 93; fax, (33) 03 20 43 65 85; e-mail,christophe.biot@ensc-lille.fr.</mods:affiliation><country wicri:rule="url">France</country><wicri:regionArea> To whom correspondence should be addressed. E.D.-C.: tel, +49-6221-54-4188; fax, +49-6221-54-5586; e-mail, elisabeth.davioud@gmx.de.C.B.: tel, (33) 03 20 43 48 93; fax, (33) 03 20 43 65 85; e-mail</wicri:regionArea></affiliation></author><author><name sortKey="Bauer, Holger" sort="Bauer, Holger" uniqKey="Bauer H" first="Holger" last="Bauer">Holger Bauer</name><affiliation wicri:level="1"><mods:affiliation>Bioinformatique Génomique et Structurale, CP 165/61, Université Libre de Bruxelles, 50 Av. F. D. Roosevelt,B-1050 Brussels, Belgium, UMR 8525 CNRS-Université Lille II-Institut Pasteur de Lille, Institut de Biologie de Lille,1 rue du Professor Calmette, BP447 59021 Lille Cedex, France, and Biochemie-Zentrum der Universität Heidelberg,Im Neuenheimer Feld 504, 69120 Heidelberg, Germany</mods:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Bioinformatique Génomique et Structurale, CP 165/61, Université Libre de Bruxelles, 50 Av. F. D. Roosevelt,B-1050 Brussels, Belgium, UMR 8525 CNRS-Université Lille II-Institut Pasteur de Lille, Institut de Biologie de Lille,1 rue du Professor Calmette, BP447 59021 Lille Cedex, France, and Biochemie-Zentrum der Universität Heidelberg,Im Neuenheimer Feld 504, 69120 Heidelberg</wicri:regionArea></affiliation><affiliation><mods:affiliation> Institut de Biologie de Lille.</mods:affiliation></affiliation><affiliation wicri:level="1"><mods:affiliation> Delegate (E.D.-C.) and Fellow (H.B.) of Centre National de laRecherche Scientifique, France in the frame of a French−Germancooperation with the University of Heidelberg, Germany.</mods:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea> Delegate (E.D.-C.) and Fellow (H.B.) of Centre National de laRecherche Scientifique, France in the frame of a French−Germancooperation with the University of Heidelberg</wicri:regionArea></affiliation><affiliation><mods:affiliation> Biochemie-Zentrum der Universität Heidelberg.</mods: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"><mods:affiliation>Bioinformatique Génomique et Structurale, CP 165/61, Université Libre de Bruxelles, 50 Av. F. D. Roosevelt,B-1050 Brussels, Belgium, UMR 8525 CNRS-Université Lille II-Institut Pasteur de Lille, Institut de Biologie de Lille,1 rue du Professor Calmette, BP447 59021 Lille Cedex, France, and Biochemie-Zentrum der Universität Heidelberg,Im Neuenheimer Feld 504, 69120 Heidelberg, Germany</mods:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Bioinformatique Génomique et Structurale, CP 165/61, Université Libre de Bruxelles, 50 Av. F. D. Roosevelt,B-1050 Brussels, Belgium, UMR 8525 CNRS-Université Lille II-Institut Pasteur de Lille, Institut de Biologie de Lille,1 rue du Professor Calmette, BP447 59021 Lille Cedex, France, and Biochemie-Zentrum der Universität Heidelberg,Im Neuenheimer Feld 504, 69120 Heidelberg</wicri:regionArea></affiliation><affiliation><mods:affiliation> Biochemie-Zentrum der Universität Heidelberg.</mods:affiliation></affiliation></author><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"><mods:affiliation>Bioinformatique Génomique et Structurale, CP 165/61, Université Libre de Bruxelles, 50 Av. F. D. Roosevelt,B-1050 Brussels, Belgium, UMR 8525 CNRS-Université Lille II-Institut Pasteur de Lille, Institut de Biologie de Lille,1 rue du Professor Calmette, BP447 59021 Lille Cedex, France, and Biochemie-Zentrum der Universität Heidelberg,Im Neuenheimer Feld 504, 69120 Heidelberg, Germany</mods:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Bioinformatique Génomique et Structurale, CP 165/61, Université Libre de Bruxelles, 50 Av. F. D. Roosevelt,B-1050 Brussels, Belgium, UMR 8525 CNRS-Université Lille II-Institut Pasteur de Lille, Institut de Biologie de Lille,1 rue du Professor Calmette, BP447 59021 Lille Cedex, France, and Biochemie-Zentrum der Universität Heidelberg,Im Neuenheimer Feld 504, 69120 Heidelberg</wicri:regionArea></affiliation><affiliation><mods:affiliation> Institut de Biologie de Lille.</mods:affiliation></affiliation><affiliation wicri:level="1"><mods:affiliation> Delegate (E.D.-C.) and Fellow (H.B.) of Centre National de laRecherche Scientifique, France in the frame of a French−Germancooperation with the University of Heidelberg, Germany.</mods:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea> Delegate (E.D.-C.) and Fellow (H.B.) of Centre National de laRecherche Scientifique, France in the frame of a French−Germancooperation with the University of Heidelberg</wicri:regionArea></affiliation><affiliation><mods:affiliation> Biochemie-Zentrum der Universität Heidelberg.</mods:affiliation></affiliation><affiliation wicri:level="1"><mods:affiliation> To whom correspondence should be addressed. E.D.-C.: tel, +49-6221-54-4188; fax, +49-6221-54-5586; e-mail, elisabeth.davioud@gmx.de.C.B.: tel, (33) 03 20 43 48 93; fax, (33) 03 20 43 65 85; e-mail,christophe.biot@ensc-lille.fr.</mods:affiliation><country wicri:rule="url">France</country><wicri:regionArea> To whom correspondence should be addressed. E.D.-C.: tel, +49-6221-54-4188; fax, +49-6221-54-5586; e-mail, elisabeth.davioud@gmx.de.C.B.: tel, (33) 03 20 43 48 93; fax, (33) 03 20 43 65 85; e-mail</wicri:regionArea></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="2004-10-26">2004</date><date when="2004-11-18">2004</date><biblScope unit="vol">47</biblScope><biblScope unit="issue">24</biblScope><biblScope unit="page" from="5972">5972</biblScope><biblScope unit="page" to="5983">5983</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">Plasmodium parasites are exposed to elevated fluxes of reactive oxygen species during intraerythrocytic life. The most important antioxidative systems are based on the glutathione reductases of the malarial parasite Plasmodium falciparum and the host erythrocyte. The development of menadione chemistry has led to the selection of the carboxylic acid 6-[2‘-(3‘-methyl)-1‘,4‘-naphthoquinolyl] hexanoic acid M5 asan inhibitor of the parasitic enzyme. As reported here, revisiting the mechanism of M5 action revealed an uncompetitive inhibition type with respect to both NADPH and glutathione disulfide. Masking the polarity of the acidic function of M5 by ester or amide bonds improved antiplasmodial activity. Bioisosteric replacement of the carboxylic function by tetrazole to increase bioavailability and to maintain comparable acidity led to improved antimalarial properties as well, but only with the cyanoethyl-protected tetrazoles. Using computed ab initio quantum methods, detailed analyses of the electronic profiles and the molecular properties evidenced the similarity of M5 and the bioisoteric tetrazole T4. The potential binding site of these molecules is discussed in light of the recently solved crystallographic structure of P. falciparum enzyme.</div></front></TEI></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/ChloroquineV1/Data/Istex/Curation
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000A31 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Istex/Curation/biblio.hfd -nk 000A31 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= ChloroquineV1
|flux= Istex
|étape= Curation
|type= RBID
|clé= ISTEX:C9C87D4357E24AFC2F532515535998AE3A5034F9
|texte= 5-Substituted Tetrazoles as Bioisosteres of Carboxylic Acids. Bioisosterism and Mechanistic Studies on Glutathione Reductase Inhibitors as Antimalarials
}}
| This area was generated with Dilib version V0.6.33. |  |