Serveur d'exploration Chloroquine

Attention, ce site est en cours de développement !
Attention, site généré par des moyens informatiques à partir de corpus bruts.
Les informations ne sont donc pas validées.

Pharmacological properties of a new antimalarial bisthiazolium salt, T3, and a corresponding prodrug, TE3.

Identifieur interne : 000182 ( Hal/Corpus ); précédent : 000181; suivant : 000183

Pharmacological properties of a new antimalarial bisthiazolium salt, T3, and a corresponding prodrug, TE3.

Auteurs : Olivier Nicolas ; Delphine Margout ; Nicolas Taudon ; Sharon Wein ; Michèle Calas ; Henri J. Vial ; Françoise M M. Bressolle

Source :

RBID : Hal:hal-00116879

Abstract

A new approach to malarial chemotherapy based on quaternary ammonium that targets membrane biogenesis during intraerythrocytic Plasmodium falciparum development has recently been developed. To increase the bioavailability, nonionic chemically modified prodrugs were synthesized. In this paper, the pharmacological properties of a bisthiazolium salt (T3) and its bioprecursor (TE3) were studied. Their antimalarial activities were determined in vitro against the growth of P. falciparum and in vivo against the growth of P. vinckei in mice. Pharmacokinetic evaluations were performed after T3 (1.3 and 3 mg/kg of body weight administered intravenously; 6.4 mg/kg administered intraperitoneally) and TE3 (1.5 and 3 mg/kg administered intravenously; 12 mg/kg administered orally) administrations to rats. After intraperitoneal administration, very low doses offer protection in a murine model of malaria (50% efficient dose [ED50] of 0.2 to 0.25 mg/kg). After oral administration, the ED50 values were 13 and 5 mg/kg for T3 and TE3, respectively. Both compounds exerted antimalarial activity in the low nanomolar range. After TE3 administration, rapid prodrug-drug conversion occurred; the mean values of the pharmacokinetic parameters for T3 were as follows: total clearance, 1 liter/h/kg; steady-state volume of distribution, 14.8 liters/kg; and elimination half-life, 12 h. After intravenous administration, T3 plasma concentrations increased in proportion to the dose. The absolute bioavailability was 72% after intraperitoneal administration (T3); it was 15% after oral administration (TE3). T3 plasma concentrations (8 nM) 24 h following oral administration of TE3 were higher than the 50% inhibitory concentrations for the most chloroquine-resistant strains of P. falciparum (6.3 nM).


Url:
DOI: 10.1128/AAC.49.9.3631-3639.2005

Links to Exploration step

Hal:hal-00116879

Le document en format XML

<record>
<TEI>
<teiHeader>
<fileDesc>
<titleStmt>
<title xml:lang="en">Pharmacological properties of a new antimalarial bisthiazolium salt, T3, and a corresponding prodrug, TE3.</title>
<author>
<name sortKey="Nicolas, Olivier" sort="Nicolas, Olivier" uniqKey="Nicolas O" first="Olivier" last="Nicolas">Olivier Nicolas</name>
<affiliation>
<hal:affiliation type="laboratory" xml:id="struct-150387" status="OLD">
<orgName>Laboratoire de Chimie des Biomolécules et de l'Environnement</orgName>
<orgName type="acronym">LCBE</orgName>
<desc>
<address>
<addrLine>Via Domitia, UPVD, 52 avenue Paul Alduy, 66860 Perpignan Cedex 9</addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://www.univ-perp.fr/fr/index.html</ref>
</desc>
<listRelation>
<relation name="EA 4215" active="#struct-101475" type="direct"></relation>
<relation name="EA 4215" active="#struct-42570" type="direct"></relation>
</listRelation>
<tutelles>
<tutelle name="EA 4215" active="#struct-101475" type="direct">
<org type="institution" xml:id="struct-101475" status="VALID">
<orgName>Université de Perpignan Via Domitia</orgName>
<orgName type="acronym">UPVD</orgName>
<desc>
<address>
<addrLine>52 avenue Paul Alduy - 66860 Perpignan Cedex 9</addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://www.univ-perp.fr/</ref>
</desc>
</org>
</tutelle>
<tutelle name="EA 4215" active="#struct-42570" type="direct">
<org type="institution" xml:id="struct-42570" status="OLD">
<orgName>Université Montpellier 1</orgName>
<orgName type="acronym">UM1</orgName>
<date type="end">2014-12-31</date>
<desc>
<address>
<addrLine>5, boulevard Henri IV - CS 19044 - 34967 Montpellier cedex</addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://www.univ-montp1.fr/</ref>
</desc>
</org>
</tutelle>
</tutelles>
</hal:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Margout, Delphine" sort="Margout, Delphine" uniqKey="Margout D" first="Delphine" last="Margout">Delphine Margout</name>
<affiliation>
<hal:affiliation type="laboratory" xml:id="struct-150387" status="OLD">
<orgName>Laboratoire de Chimie des Biomolécules et de l'Environnement</orgName>
<orgName type="acronym">LCBE</orgName>
<desc>
<address>
<addrLine>Via Domitia, UPVD, 52 avenue Paul Alduy, 66860 Perpignan Cedex 9</addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://www.univ-perp.fr/fr/index.html</ref>
</desc>
<listRelation>
<relation name="EA 4215" active="#struct-101475" type="direct"></relation>
<relation name="EA 4215" active="#struct-42570" type="direct"></relation>
</listRelation>
<tutelles>
<tutelle name="EA 4215" active="#struct-101475" type="direct">
<org type="institution" xml:id="struct-101475" status="VALID">
<orgName>Université de Perpignan Via Domitia</orgName>
<orgName type="acronym">UPVD</orgName>
<desc>
<address>
<addrLine>52 avenue Paul Alduy - 66860 Perpignan Cedex 9</addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://www.univ-perp.fr/</ref>
</desc>
</org>
</tutelle>
<tutelle name="EA 4215" active="#struct-42570" type="direct">
<org type="institution" xml:id="struct-42570" status="OLD">
<orgName>Université Montpellier 1</orgName>
<orgName type="acronym">UM1</orgName>
<date type="end">2014-12-31</date>
<desc>
<address>
<addrLine>5, boulevard Henri IV - CS 19044 - 34967 Montpellier cedex</addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://www.univ-montp1.fr/</ref>
</desc>
</org>
</tutelle>
</tutelles>
</hal:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Taudon, Nicolas" sort="Taudon, Nicolas" uniqKey="Taudon N" first="Nicolas" last="Taudon">Nicolas Taudon</name>
<affiliation>
<hal:affiliation type="laboratory" xml:id="struct-150387" status="OLD">
<orgName>Laboratoire de Chimie des Biomolécules et de l'Environnement</orgName>
<orgName type="acronym">LCBE</orgName>
<desc>
<address>
<addrLine>Via Domitia, UPVD, 52 avenue Paul Alduy, 66860 Perpignan Cedex 9</addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://www.univ-perp.fr/fr/index.html</ref>
</desc>
<listRelation>
<relation name="EA 4215" active="#struct-101475" type="direct"></relation>
<relation name="EA 4215" active="#struct-42570" type="direct"></relation>
</listRelation>
<tutelles>
<tutelle name="EA 4215" active="#struct-101475" type="direct">
<org type="institution" xml:id="struct-101475" status="VALID">
<orgName>Université de Perpignan Via Domitia</orgName>
<orgName type="acronym">UPVD</orgName>
<desc>
<address>
<addrLine>52 avenue Paul Alduy - 66860 Perpignan Cedex 9</addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://www.univ-perp.fr/</ref>
</desc>
</org>
</tutelle>
<tutelle name="EA 4215" active="#struct-42570" type="direct">
<org type="institution" xml:id="struct-42570" status="OLD">
<orgName>Université Montpellier 1</orgName>
<orgName type="acronym">UM1</orgName>
<date type="end">2014-12-31</date>
<desc>
<address>
<addrLine>5, boulevard Henri IV - CS 19044 - 34967 Montpellier cedex</addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://www.univ-montp1.fr/</ref>
</desc>
</org>
</tutelle>
</tutelles>
</hal:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Wein, Sharon" sort="Wein, Sharon" uniqKey="Wein S" first="Sharon" last="Wein">Sharon Wein</name>
<affiliation>
<hal:affiliation type="laboratory" xml:id="struct-716" status="OLD">
<orgName>Dynamique moléculaire des interactions membranaires</orgName>
<orgName type="acronym">DMIM</orgName>
<desc>
<address>
<addrLine>BT 24 CC 107 Place Eugène Bataillon 34095 MONTPELLIER CEDEX 5</addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://www.dbs.univ-montp2.fr/umr5539/</ref>
</desc>
<listRelation>
<relation active="#struct-92690" type="direct"></relation>
<relation name="UMR5539" active="#struct-441569" type="direct"></relation>
</listRelation>
<tutelles>
<tutelle active="#struct-92690" type="direct">
<org type="institution" xml:id="struct-92690" status="OLD">
<orgName>Université Montpellier 2 - Sciences et Techniques</orgName>
<orgName type="acronym">UM2</orgName>
<date type="end">2014-12-31</date>
<desc>
<address>
<addrLine>Place Eugène Bataillon - 34095 Montpellier cedex 5</addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://www.univ-montp2.fr/</ref>
</desc>
</org>
</tutelle>
<tutelle name="UMR5539" active="#struct-441569" type="direct">
<org type="institution" xml:id="struct-441569" status="VALID">
<idno type="IdRef">02636817X</idno>
<idno type="ISNI">0000000122597504</idno>
<orgName>Centre National de la Recherche Scientifique</orgName>
<orgName type="acronym">CNRS</orgName>
<date type="start">1939-10-19</date>
<desc>
<address>
<country key="FR"></country>
</address>
<ref type="url">http://www.cnrs.fr/</ref>
</desc>
</org>
</tutelle>
</tutelles>
</hal:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Calas, Michele" sort="Calas, Michele" uniqKey="Calas M" first="Michèle" last="Calas">Michèle Calas</name>
<affiliation>
<hal:affiliation type="laboratory" xml:id="struct-25112" status="OLD">
<orgName>Laboratoire des Amino-acides Peptides et Protéines</orgName>
<orgName type="acronym">LAPP</orgName>
<desc>
<address>
<addrLine>15, Avenue Charles Flahault BP 1441 34093 Montpellier Cédex 5, France</addrLine>
<country key="FR"></country>
</address>
</desc>
<listRelation>
<relation active="#struct-42570" type="direct"></relation>
<relation active="#struct-92690" type="direct"></relation>
<relation name="UMR5810" active="#struct-441569" type="direct"></relation>
</listRelation>
<tutelles>
<tutelle active="#struct-42570" type="direct">
<org type="institution" xml:id="struct-42570" status="OLD">
<orgName>Université Montpellier 1</orgName>
<orgName type="acronym">UM1</orgName>
<date type="end">2014-12-31</date>
<desc>
<address>
<addrLine>5, boulevard Henri IV - CS 19044 - 34967 Montpellier cedex</addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://www.univ-montp1.fr/</ref>
</desc>
</org>
</tutelle>
<tutelle active="#struct-92690" type="direct">
<org type="institution" xml:id="struct-92690" status="OLD">
<orgName>Université Montpellier 2 - Sciences et Techniques</orgName>
<orgName type="acronym">UM2</orgName>
<date type="end">2014-12-31</date>
<desc>
<address>
<addrLine>Place Eugène Bataillon - 34095 Montpellier cedex 5</addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://www.univ-montp2.fr/</ref>
</desc>
</org>
</tutelle>
<tutelle name="UMR5810" active="#struct-441569" type="direct">
<org type="institution" xml:id="struct-441569" status="VALID">
<idno type="IdRef">02636817X</idno>
<idno type="ISNI">0000000122597504</idno>
<orgName>Centre National de la Recherche Scientifique</orgName>
<orgName type="acronym">CNRS</orgName>
<date type="start">1939-10-19</date>
<desc>
<address>
<country key="FR"></country>
</address>
<ref type="url">http://www.cnrs.fr/</ref>
</desc>
</org>
</tutelle>
</tutelles>
</hal:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Vial, Henri J" sort="Vial, Henri J" uniqKey="Vial H" first="Henri J" last="Vial">Henri J. Vial</name>
<affiliation>
<hal:affiliation type="laboratory" xml:id="struct-716" status="OLD">
<orgName>Dynamique moléculaire des interactions membranaires</orgName>
<orgName type="acronym">DMIM</orgName>
<desc>
<address>
<addrLine>BT 24 CC 107 Place Eugène Bataillon 34095 MONTPELLIER CEDEX 5</addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://www.dbs.univ-montp2.fr/umr5539/</ref>
</desc>
<listRelation>
<relation active="#struct-92690" type="direct"></relation>
<relation name="UMR5539" active="#struct-441569" type="direct"></relation>
</listRelation>
<tutelles>
<tutelle active="#struct-92690" type="direct">
<org type="institution" xml:id="struct-92690" status="OLD">
<orgName>Université Montpellier 2 - Sciences et Techniques</orgName>
<orgName type="acronym">UM2</orgName>
<date type="end">2014-12-31</date>
<desc>
<address>
<addrLine>Place Eugène Bataillon - 34095 Montpellier cedex 5</addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://www.univ-montp2.fr/</ref>
</desc>
</org>
</tutelle>
<tutelle name="UMR5539" active="#struct-441569" type="direct">
<org type="institution" xml:id="struct-441569" status="VALID">
<idno type="IdRef">02636817X</idno>
<idno type="ISNI">0000000122597504</idno>
<orgName>Centre National de la Recherche Scientifique</orgName>
<orgName type="acronym">CNRS</orgName>
<date type="start">1939-10-19</date>
<desc>
<address>
<country key="FR"></country>
</address>
<ref type="url">http://www.cnrs.fr/</ref>
</desc>
</org>
</tutelle>
</tutelles>
</hal:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Bressolle, Francoise M M" sort="Bressolle, Francoise M M" uniqKey="Bressolle F" first="Françoise M M" last="Bressolle">Françoise M M. Bressolle</name>
<affiliation>
<hal:affiliation type="laboratory" xml:id="struct-150387" status="OLD">
<orgName>Laboratoire de Chimie des Biomolécules et de l'Environnement</orgName>
<orgName type="acronym">LCBE</orgName>
<desc>
<address>
<addrLine>Via Domitia, UPVD, 52 avenue Paul Alduy, 66860 Perpignan Cedex 9</addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://www.univ-perp.fr/fr/index.html</ref>
</desc>
<listRelation>
<relation name="EA 4215" active="#struct-101475" type="direct"></relation>
<relation name="EA 4215" active="#struct-42570" type="direct"></relation>
</listRelation>
<tutelles>
<tutelle name="EA 4215" active="#struct-101475" type="direct">
<org type="institution" xml:id="struct-101475" status="VALID">
<orgName>Université de Perpignan Via Domitia</orgName>
<orgName type="acronym">UPVD</orgName>
<desc>
<address>
<addrLine>52 avenue Paul Alduy - 66860 Perpignan Cedex 9</addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://www.univ-perp.fr/</ref>
</desc>
</org>
</tutelle>
<tutelle name="EA 4215" active="#struct-42570" type="direct">
<org type="institution" xml:id="struct-42570" status="OLD">
<orgName>Université Montpellier 1</orgName>
<orgName type="acronym">UM1</orgName>
<date type="end">2014-12-31</date>
<desc>
<address>
<addrLine>5, boulevard Henri IV - CS 19044 - 34967 Montpellier cedex</addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://www.univ-montp1.fr/</ref>
</desc>
</org>
</tutelle>
</tutelles>
</hal:affiliation>
</affiliation>
</author>
</titleStmt>
<publicationStmt>
<idno type="wicri:source">HAL</idno>
<idno type="RBID">Hal:hal-00116879</idno>
<idno type="halId">hal-00116879</idno>
<idno type="halUri">https://hal.archives-ouvertes.fr/hal-00116879</idno>
<idno type="url">https://hal.archives-ouvertes.fr/hal-00116879</idno>
<idno type="doi">10.1128/AAC.49.9.3631-3639.2005</idno>
<date when="2005-09">2005-09</date>
<idno type="wicri:Area/Hal/Corpus">000182</idno>
</publicationStmt>
<sourceDesc>
<biblStruct>
<analytic>
<title xml:lang="en">Pharmacological properties of a new antimalarial bisthiazolium salt, T3, and a corresponding prodrug, TE3.</title>
<author>
<name sortKey="Nicolas, Olivier" sort="Nicolas, Olivier" uniqKey="Nicolas O" first="Olivier" last="Nicolas">Olivier Nicolas</name>
<affiliation>
<hal:affiliation type="laboratory" xml:id="struct-150387" status="OLD">
<orgName>Laboratoire de Chimie des Biomolécules et de l'Environnement</orgName>
<orgName type="acronym">LCBE</orgName>
<desc>
<address>
<addrLine>Via Domitia, UPVD, 52 avenue Paul Alduy, 66860 Perpignan Cedex 9</addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://www.univ-perp.fr/fr/index.html</ref>
</desc>
<listRelation>
<relation name="EA 4215" active="#struct-101475" type="direct"></relation>
<relation name="EA 4215" active="#struct-42570" type="direct"></relation>
</listRelation>
<tutelles>
<tutelle name="EA 4215" active="#struct-101475" type="direct">
<org type="institution" xml:id="struct-101475" status="VALID">
<orgName>Université de Perpignan Via Domitia</orgName>
<orgName type="acronym">UPVD</orgName>
<desc>
<address>
<addrLine>52 avenue Paul Alduy - 66860 Perpignan Cedex 9</addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://www.univ-perp.fr/</ref>
</desc>
</org>
</tutelle>
<tutelle name="EA 4215" active="#struct-42570" type="direct">
<org type="institution" xml:id="struct-42570" status="OLD">
<orgName>Université Montpellier 1</orgName>
<orgName type="acronym">UM1</orgName>
<date type="end">2014-12-31</date>
<desc>
<address>
<addrLine>5, boulevard Henri IV - CS 19044 - 34967 Montpellier cedex</addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://www.univ-montp1.fr/</ref>
</desc>
</org>
</tutelle>
</tutelles>
</hal:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Margout, Delphine" sort="Margout, Delphine" uniqKey="Margout D" first="Delphine" last="Margout">Delphine Margout</name>
<affiliation>
<hal:affiliation type="laboratory" xml:id="struct-150387" status="OLD">
<orgName>Laboratoire de Chimie des Biomolécules et de l'Environnement</orgName>
<orgName type="acronym">LCBE</orgName>
<desc>
<address>
<addrLine>Via Domitia, UPVD, 52 avenue Paul Alduy, 66860 Perpignan Cedex 9</addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://www.univ-perp.fr/fr/index.html</ref>
</desc>
<listRelation>
<relation name="EA 4215" active="#struct-101475" type="direct"></relation>
<relation name="EA 4215" active="#struct-42570" type="direct"></relation>
</listRelation>
<tutelles>
<tutelle name="EA 4215" active="#struct-101475" type="direct">
<org type="institution" xml:id="struct-101475" status="VALID">
<orgName>Université de Perpignan Via Domitia</orgName>
<orgName type="acronym">UPVD</orgName>
<desc>
<address>
<addrLine>52 avenue Paul Alduy - 66860 Perpignan Cedex 9</addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://www.univ-perp.fr/</ref>
</desc>
</org>
</tutelle>
<tutelle name="EA 4215" active="#struct-42570" type="direct">
<org type="institution" xml:id="struct-42570" status="OLD">
<orgName>Université Montpellier 1</orgName>
<orgName type="acronym">UM1</orgName>
<date type="end">2014-12-31</date>
<desc>
<address>
<addrLine>5, boulevard Henri IV - CS 19044 - 34967 Montpellier cedex</addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://www.univ-montp1.fr/</ref>
</desc>
</org>
</tutelle>
</tutelles>
</hal:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Taudon, Nicolas" sort="Taudon, Nicolas" uniqKey="Taudon N" first="Nicolas" last="Taudon">Nicolas Taudon</name>
<affiliation>
<hal:affiliation type="laboratory" xml:id="struct-150387" status="OLD">
<orgName>Laboratoire de Chimie des Biomolécules et de l'Environnement</orgName>
<orgName type="acronym">LCBE</orgName>
<desc>
<address>
<addrLine>Via Domitia, UPVD, 52 avenue Paul Alduy, 66860 Perpignan Cedex 9</addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://www.univ-perp.fr/fr/index.html</ref>
</desc>
<listRelation>
<relation name="EA 4215" active="#struct-101475" type="direct"></relation>
<relation name="EA 4215" active="#struct-42570" type="direct"></relation>
</listRelation>
<tutelles>
<tutelle name="EA 4215" active="#struct-101475" type="direct">
<org type="institution" xml:id="struct-101475" status="VALID">
<orgName>Université de Perpignan Via Domitia</orgName>
<orgName type="acronym">UPVD</orgName>
<desc>
<address>
<addrLine>52 avenue Paul Alduy - 66860 Perpignan Cedex 9</addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://www.univ-perp.fr/</ref>
</desc>
</org>
</tutelle>
<tutelle name="EA 4215" active="#struct-42570" type="direct">
<org type="institution" xml:id="struct-42570" status="OLD">
<orgName>Université Montpellier 1</orgName>
<orgName type="acronym">UM1</orgName>
<date type="end">2014-12-31</date>
<desc>
<address>
<addrLine>5, boulevard Henri IV - CS 19044 - 34967 Montpellier cedex</addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://www.univ-montp1.fr/</ref>
</desc>
</org>
</tutelle>
</tutelles>
</hal:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Wein, Sharon" sort="Wein, Sharon" uniqKey="Wein S" first="Sharon" last="Wein">Sharon Wein</name>
<affiliation>
<hal:affiliation type="laboratory" xml:id="struct-716" status="OLD">
<orgName>Dynamique moléculaire des interactions membranaires</orgName>
<orgName type="acronym">DMIM</orgName>
<desc>
<address>
<addrLine>BT 24 CC 107 Place Eugène Bataillon 34095 MONTPELLIER CEDEX 5</addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://www.dbs.univ-montp2.fr/umr5539/</ref>
</desc>
<listRelation>
<relation active="#struct-92690" type="direct"></relation>
<relation name="UMR5539" active="#struct-441569" type="direct"></relation>
</listRelation>
<tutelles>
<tutelle active="#struct-92690" type="direct">
<org type="institution" xml:id="struct-92690" status="OLD">
<orgName>Université Montpellier 2 - Sciences et Techniques</orgName>
<orgName type="acronym">UM2</orgName>
<date type="end">2014-12-31</date>
<desc>
<address>
<addrLine>Place Eugène Bataillon - 34095 Montpellier cedex 5</addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://www.univ-montp2.fr/</ref>
</desc>
</org>
</tutelle>
<tutelle name="UMR5539" active="#struct-441569" type="direct">
<org type="institution" xml:id="struct-441569" status="VALID">
<idno type="IdRef">02636817X</idno>
<idno type="ISNI">0000000122597504</idno>
<orgName>Centre National de la Recherche Scientifique</orgName>
<orgName type="acronym">CNRS</orgName>
<date type="start">1939-10-19</date>
<desc>
<address>
<country key="FR"></country>
</address>
<ref type="url">http://www.cnrs.fr/</ref>
</desc>
</org>
</tutelle>
</tutelles>
</hal:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Calas, Michele" sort="Calas, Michele" uniqKey="Calas M" first="Michèle" last="Calas">Michèle Calas</name>
<affiliation>
<hal:affiliation type="laboratory" xml:id="struct-25112" status="OLD">
<orgName>Laboratoire des Amino-acides Peptides et Protéines</orgName>
<orgName type="acronym">LAPP</orgName>
<desc>
<address>
<addrLine>15, Avenue Charles Flahault BP 1441 34093 Montpellier Cédex 5, France</addrLine>
<country key="FR"></country>
</address>
</desc>
<listRelation>
<relation active="#struct-42570" type="direct"></relation>
<relation active="#struct-92690" type="direct"></relation>
<relation name="UMR5810" active="#struct-441569" type="direct"></relation>
</listRelation>
<tutelles>
<tutelle active="#struct-42570" type="direct">
<org type="institution" xml:id="struct-42570" status="OLD">
<orgName>Université Montpellier 1</orgName>
<orgName type="acronym">UM1</orgName>
<date type="end">2014-12-31</date>
<desc>
<address>
<addrLine>5, boulevard Henri IV - CS 19044 - 34967 Montpellier cedex</addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://www.univ-montp1.fr/</ref>
</desc>
</org>
</tutelle>
<tutelle active="#struct-92690" type="direct">
<org type="institution" xml:id="struct-92690" status="OLD">
<orgName>Université Montpellier 2 - Sciences et Techniques</orgName>
<orgName type="acronym">UM2</orgName>
<date type="end">2014-12-31</date>
<desc>
<address>
<addrLine>Place Eugène Bataillon - 34095 Montpellier cedex 5</addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://www.univ-montp2.fr/</ref>
</desc>
</org>
</tutelle>
<tutelle name="UMR5810" active="#struct-441569" type="direct">
<org type="institution" xml:id="struct-441569" status="VALID">
<idno type="IdRef">02636817X</idno>
<idno type="ISNI">0000000122597504</idno>
<orgName>Centre National de la Recherche Scientifique</orgName>
<orgName type="acronym">CNRS</orgName>
<date type="start">1939-10-19</date>
<desc>
<address>
<country key="FR"></country>
</address>
<ref type="url">http://www.cnrs.fr/</ref>
</desc>
</org>
</tutelle>
</tutelles>
</hal:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Vial, Henri J" sort="Vial, Henri J" uniqKey="Vial H" first="Henri J" last="Vial">Henri J. Vial</name>
<affiliation>
<hal:affiliation type="laboratory" xml:id="struct-716" status="OLD">
<orgName>Dynamique moléculaire des interactions membranaires</orgName>
<orgName type="acronym">DMIM</orgName>
<desc>
<address>
<addrLine>BT 24 CC 107 Place Eugène Bataillon 34095 MONTPELLIER CEDEX 5</addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://www.dbs.univ-montp2.fr/umr5539/</ref>
</desc>
<listRelation>
<relation active="#struct-92690" type="direct"></relation>
<relation name="UMR5539" active="#struct-441569" type="direct"></relation>
</listRelation>
<tutelles>
<tutelle active="#struct-92690" type="direct">
<org type="institution" xml:id="struct-92690" status="OLD">
<orgName>Université Montpellier 2 - Sciences et Techniques</orgName>
<orgName type="acronym">UM2</orgName>
<date type="end">2014-12-31</date>
<desc>
<address>
<addrLine>Place Eugène Bataillon - 34095 Montpellier cedex 5</addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://www.univ-montp2.fr/</ref>
</desc>
</org>
</tutelle>
<tutelle name="UMR5539" active="#struct-441569" type="direct">
<org type="institution" xml:id="struct-441569" status="VALID">
<idno type="IdRef">02636817X</idno>
<idno type="ISNI">0000000122597504</idno>
<orgName>Centre National de la Recherche Scientifique</orgName>
<orgName type="acronym">CNRS</orgName>
<date type="start">1939-10-19</date>
<desc>
<address>
<country key="FR"></country>
</address>
<ref type="url">http://www.cnrs.fr/</ref>
</desc>
</org>
</tutelle>
</tutelles>
</hal:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Bressolle, Francoise M M" sort="Bressolle, Francoise M M" uniqKey="Bressolle F" first="Françoise M M" last="Bressolle">Françoise M M. Bressolle</name>
<affiliation>
<hal:affiliation type="laboratory" xml:id="struct-150387" status="OLD">
<orgName>Laboratoire de Chimie des Biomolécules et de l'Environnement</orgName>
<orgName type="acronym">LCBE</orgName>
<desc>
<address>
<addrLine>Via Domitia, UPVD, 52 avenue Paul Alduy, 66860 Perpignan Cedex 9</addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://www.univ-perp.fr/fr/index.html</ref>
</desc>
<listRelation>
<relation name="EA 4215" active="#struct-101475" type="direct"></relation>
<relation name="EA 4215" active="#struct-42570" type="direct"></relation>
</listRelation>
<tutelles>
<tutelle name="EA 4215" active="#struct-101475" type="direct">
<org type="institution" xml:id="struct-101475" status="VALID">
<orgName>Université de Perpignan Via Domitia</orgName>
<orgName type="acronym">UPVD</orgName>
<desc>
<address>
<addrLine>52 avenue Paul Alduy - 66860 Perpignan Cedex 9</addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://www.univ-perp.fr/</ref>
</desc>
</org>
</tutelle>
<tutelle name="EA 4215" active="#struct-42570" type="direct">
<org type="institution" xml:id="struct-42570" status="OLD">
<orgName>Université Montpellier 1</orgName>
<orgName type="acronym">UM1</orgName>
<date type="end">2014-12-31</date>
<desc>
<address>
<addrLine>5, boulevard Henri IV - CS 19044 - 34967 Montpellier cedex</addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://www.univ-montp1.fr/</ref>
</desc>
</org>
</tutelle>
</tutelles>
</hal:affiliation>
</affiliation>
</author>
</analytic>
<idno type="DOI">10.1128/AAC.49.9.3631-3639.2005</idno>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass></textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<p>A new approach to malarial chemotherapy based on quaternary ammonium that targets membrane biogenesis during intraerythrocytic Plasmodium falciparum development has recently been developed. To increase the bioavailability, nonionic chemically modified prodrugs were synthesized. In this paper, the pharmacological properties of a bisthiazolium salt (T3) and its bioprecursor (TE3) were studied. Their antimalarial activities were determined in vitro against the growth of P. falciparum and in vivo against the growth of P. vinckei in mice. Pharmacokinetic evaluations were performed after T3 (1.3 and 3 mg/kg of body weight administered intravenously; 6.4 mg/kg administered intraperitoneally) and TE3 (1.5 and 3 mg/kg administered intravenously; 12 mg/kg administered orally) administrations to rats. After intraperitoneal administration, very low doses offer protection in a murine model of malaria (50% efficient dose [ED50] of 0.2 to 0.25 mg/kg). After oral administration, the ED50 values were 13 and 5 mg/kg for T3 and TE3, respectively. Both compounds exerted antimalarial activity in the low nanomolar range. After TE3 administration, rapid prodrug-drug conversion occurred; the mean values of the pharmacokinetic parameters for T3 were as follows: total clearance, 1 liter/h/kg; steady-state volume of distribution, 14.8 liters/kg; and elimination half-life, 12 h. After intravenous administration, T3 plasma concentrations increased in proportion to the dose. The absolute bioavailability was 72% after intraperitoneal administration (T3); it was 15% after oral administration (TE3). T3 plasma concentrations (8 nM) 24 h following oral administration of TE3 were higher than the 50% inhibitory concentrations for the most chloroquine-resistant strains of P. falciparum (6.3 nM).</p>
</div>
</front>
</TEI>
<hal api="V3">
<titleStmt>
<title xml:lang="en">Pharmacological properties of a new antimalarial bisthiazolium salt, T3, and a corresponding prodrug, TE3.</title>
<author role="aut">
<persName>
<forename type="first">Olivier</forename>
<surname>Nicolas</surname>
</persName>
<idno type="halauthorid">148806</idno>
<affiliation ref="#struct-150387"></affiliation>
</author>
<author role="aut">
<persName>
<forename type="first">Delphine</forename>
<surname>Margout</surname>
</persName>
<idno type="halauthorid">148807</idno>
<affiliation ref="#struct-150387"></affiliation>
</author>
<author role="aut">
<persName>
<forename type="first">Nicolas</forename>
<surname>Taudon</surname>
</persName>
<idno type="halauthorid">148808</idno>
<affiliation ref="#struct-150387"></affiliation>
</author>
<author role="aut">
<persName>
<forename type="first">Sharon</forename>
<surname>Wein</surname>
</persName>
<idno type="halauthorid">148774</idno>
<affiliation ref="#struct-716"></affiliation>
</author>
<author role="aut">
<persName>
<forename type="first">Michèle</forename>
<surname>Calas</surname>
</persName>
<idno type="halauthorid">148779</idno>
<affiliation ref="#struct-25112"></affiliation>
</author>
<author role="aut">
<persName>
<forename type="first">Henri J</forename>
<surname>Vial</surname>
</persName>
<idno type="halauthorid">148781</idno>
<affiliation ref="#struct-716"></affiliation>
</author>
<author role="aut">
<persName>
<forename type="first">Françoise M M</forename>
<surname>Bressolle</surname>
</persName>
<idno type="halauthorid">148809</idno>
<affiliation ref="#struct-150387"></affiliation>
</author>
<editor role="depositor">
<persName>
<forename>Michèle</forename>
<surname>Calas</surname>
</persName>
<email type="md5">8c58733fe8d9d5035689606e2fd2a2dd</email>
<email type="domain">univ-montp2.fr</email>
</editor>
</titleStmt>
<editionStmt>
<edition n="v1" type="current">
<date type="whenSubmitted">2006-11-28 15:31:58</date>
<date type="whenModified">2019-10-11 01:15:27</date>
<date type="whenReleased">2006-11-28 15:31:58</date>
<date type="whenProduced">2005-09</date>
<ref type="externalLink" target="https://aac.asm.org/content/49/9/3631.full.pdf"></ref>
</edition>
<respStmt>
<resp>contributor</resp>
<name key="103870">
<persName>
<forename>Michèle</forename>
<surname>Calas</surname>
</persName>
<email type="md5">8c58733fe8d9d5035689606e2fd2a2dd</email>
<email type="domain">univ-montp2.fr</email>
</name>
</respStmt>
</editionStmt>
<publicationStmt>
<distributor>CCSD</distributor>
<idno type="halId">hal-00116879</idno>
<idno type="halUri">https://hal.archives-ouvertes.fr/hal-00116879</idno>
<idno type="halBibtex">nicolas:hal-00116879</idno>
<idno type="halRefHtml">Antimicrob Agents Chemother, 2005, 49 (9), pp.3631-9. ⟨10.1128/AAC.49.9.3631-3639.2005⟩</idno>
<idno type="halRef">Antimicrob Agents Chemother, 2005, 49 (9), pp.3631-9. ⟨10.1128/AAC.49.9.3631-3639.2005⟩</idno>
</publicationStmt>
<seriesStmt>
<idno type="stamp" n="CNRS">CNRS - Centre national de la recherche scientifique</idno>
<idno type="stamp" n="UNIV-PERP">Université de Perpignan Via Domitia</idno>
<idno type="stamp" n="AGROPOLIS">Agropolis</idno>
<idno type="stamp" n="CRIOBE">Centre de Recherches Insulaires et Observatoire de l'Environnement</idno>
</seriesStmt>
<notesStmt>
<note type="audience" n="1">Not set</note>
<note type="popular" n="0">No</note>
<note type="peer" n="1">Yes</note>
</notesStmt>
<sourceDesc>
<biblStruct>
<analytic>
<title xml:lang="en">Pharmacological properties of a new antimalarial bisthiazolium salt, T3, and a corresponding prodrug, TE3.</title>
<author role="aut">
<persName>
<forename type="first">Olivier</forename>
<surname>Nicolas</surname>
</persName>
<idno type="halauthorid">148806</idno>
<affiliation ref="#struct-150387"></affiliation>
</author>
<author role="aut">
<persName>
<forename type="first">Delphine</forename>
<surname>Margout</surname>
</persName>
<idno type="halauthorid">148807</idno>
<affiliation ref="#struct-150387"></affiliation>
</author>
<author role="aut">
<persName>
<forename type="first">Nicolas</forename>
<surname>Taudon</surname>
</persName>
<idno type="halauthorid">148808</idno>
<affiliation ref="#struct-150387"></affiliation>
</author>
<author role="aut">
<persName>
<forename type="first">Sharon</forename>
<surname>Wein</surname>
</persName>
<idno type="halauthorid">148774</idno>
<affiliation ref="#struct-716"></affiliation>
</author>
<author role="aut">
<persName>
<forename type="first">Michèle</forename>
<surname>Calas</surname>
</persName>
<idno type="halauthorid">148779</idno>
<affiliation ref="#struct-25112"></affiliation>
</author>
<author role="aut">
<persName>
<forename type="first">Henri J</forename>
<surname>Vial</surname>
</persName>
<idno type="halauthorid">148781</idno>
<affiliation ref="#struct-716"></affiliation>
</author>
<author role="aut">
<persName>
<forename type="first">Françoise M M</forename>
<surname>Bressolle</surname>
</persName>
<idno type="halauthorid">148809</idno>
<affiliation ref="#struct-150387"></affiliation>
</author>
</analytic>
<monogr>
<idno type="halJournalId" status="INCOMING">25221</idno>
<title level="j">Antimicrob Agents Chemother</title>
<imprint>
<biblScope unit="volume">49</biblScope>
<biblScope unit="issue">9</biblScope>
<biblScope unit="pp">3631-9</biblScope>
<date type="datePub">2005-09</date>
<date type="dateEpub">2006-11-10</date>
</imprint>
</monogr>
<idno type="doi">10.1128/AAC.49.9.3631-3639.2005</idno>
<idno type="pubmed">16127032</idno>
</biblStruct>
</sourceDesc>
<profileDesc>
<langUsage>
<language ident="en">English</language>
</langUsage>
<textClass>
<classCode scheme="mesh">Animals</classCode>
<classCode scheme="mesh">Antimalarials</classCode>
<classCode scheme="mesh">Plasmodium falciparum</classCode>
<classCode scheme="mesh">Prodrugs</classCode>
<classCode scheme="mesh">Rats</classCode>
<classCode scheme="mesh">Rats, Sprague-Dawley</classCode>
<classCode scheme="mesh">Research Support, Non-U.S. Gov't</classCode>
<classCode scheme="mesh">Thiazoles</classCode>
<classCode scheme="mesh">Bayes Theorem</classCode>
<classCode scheme="mesh">Female</classCode>
<classCode scheme="mesh">Injections, Intraperitoneal</classCode>
<classCode scheme="mesh">Injections, Intravenous</classCode>
<classCode scheme="mesh">Malaria</classCode>
<classCode scheme="mesh">Mice</classCode>
<classCode scheme="mesh">Models, Biological</classCode>
<classCode scheme="mesh">Plasmodium</classCode>
<classCode scheme="halDomain" n="sdv.bbm.bc">Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM]</classCode>
<classCode scheme="halTypology" n="ART">Journal articles</classCode>
</textClass>
<abstract xml:lang="en">
<p>A new approach to malarial chemotherapy based on quaternary ammonium that targets membrane biogenesis during intraerythrocytic Plasmodium falciparum development has recently been developed. To increase the bioavailability, nonionic chemically modified prodrugs were synthesized. In this paper, the pharmacological properties of a bisthiazolium salt (T3) and its bioprecursor (TE3) were studied. Their antimalarial activities were determined in vitro against the growth of P. falciparum and in vivo against the growth of P. vinckei in mice. Pharmacokinetic evaluations were performed after T3 (1.3 and 3 mg/kg of body weight administered intravenously; 6.4 mg/kg administered intraperitoneally) and TE3 (1.5 and 3 mg/kg administered intravenously; 12 mg/kg administered orally) administrations to rats. After intraperitoneal administration, very low doses offer protection in a murine model of malaria (50% efficient dose [ED50] of 0.2 to 0.25 mg/kg). After oral administration, the ED50 values were 13 and 5 mg/kg for T3 and TE3, respectively. Both compounds exerted antimalarial activity in the low nanomolar range. After TE3 administration, rapid prodrug-drug conversion occurred; the mean values of the pharmacokinetic parameters for T3 were as follows: total clearance, 1 liter/h/kg; steady-state volume of distribution, 14.8 liters/kg; and elimination half-life, 12 h. After intravenous administration, T3 plasma concentrations increased in proportion to the dose. The absolute bioavailability was 72% after intraperitoneal administration (T3); it was 15% after oral administration (TE3). T3 plasma concentrations (8 nM) 24 h following oral administration of TE3 were higher than the 50% inhibitory concentrations for the most chloroquine-resistant strains of P. falciparum (6.3 nM).</p>
</abstract>
</profileDesc>
</hal>
</record>

Pour manipuler ce document sous Unix (Dilib)

EXPLOR_STEP=$WICRI_ROOT/Sante/explor/ChloroquineV1/Data/Hal/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000182 | SxmlIndent | more

Ou

HfdSelect -h $EXPLOR_AREA/Data/Hal/Corpus/biblio.hfd -nk 000182 | SxmlIndent | more

Pour mettre un lien sur cette page dans le réseau Wicri

{{Explor lien
   |wiki=    Sante
   |area=    ChloroquineV1
   |flux=    Hal
   |étape=   Corpus
   |type=    RBID
   |clé=     Hal:hal-00116879
   |texte=   Pharmacological properties of a new antimalarial bisthiazolium salt, T3, and a corresponding prodrug, TE3.
}}

Wicri

This area was generated with Dilib version V0.6.33.
Data generation: Wed Mar 25 22:43:59 2020. Site generation: Sun Jan 31 12:44:45 2021