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Dihydroethanoanthracene derivatives reverse in vitro quinoline resistance in Plasmodium falciparum malaria.

Identifieur interne : 000286 ( France/Analysis ); précédent : 000285; suivant : 000287

Dihydroethanoanthracene derivatives reverse in vitro quinoline resistance in Plasmodium falciparum malaria.

Auteurs : Maud Henry [France] ; Sandrine Alibert [France] ; Meili Baragatti [France] ; Joel Mosnier [France] ; Eric Baret [France] ; Rémy Amalvict [France] ; Eric Legrand ; Thierry Fusai [France] ; Jacques Barbe [France] ; Christophe Rogier [France] ; Jean-Marie Pagès [France] ; Bruno Pradines [France]

Source :

RBID : Hal:pasteur-00590982

English descriptors

Abstract

The capacity of ten molecules for reversing resistance in Plasmodium falciparum in vitro to quinoline antimalarial drugs, such as chloroquine (CQ), quinine (QN), mefloquine (MQ) and monodesethylamodiaquine (MDAQ), was assessed against 27 Plasmodium falciparum isolates. Four of these compounds were 9,10-dihydroethanoanthracene derivatives (DEAs). These DEAs reversed 75 to 92% of the CQ resistant strains. These synthetic compounds were more effective in combination with CQ than verapamil, ketotifen, chlorpromazine, reserpine or nicardipine, which reversed less than 50% of the CQ resistant strains. DEAs significantly reversed 67 to 100% of MDAQ resistant parasites. These compounds were more effective in combination with MDAQ than ketotifen (60% of reversal), chlorpromazine (45%), verapamil (33%), reserpine (30%) or nicardipine (9%). The reversal activity of MQ resistance was less pronounced, regardless of the molecule tested, and was homogeneous with a rate ranging from 42% for ketotifen to 58% for reserpine, nicardipine, verapamil and cyproheptadine. The four DEAs significantly reversed 50 to 55% of the parasites resistant to MQ. Fifty-six to 78 % of the QN resistant parasites were reversed by the synthetic DEAs. There were few differences in the rate of reversal activity on QN resistant strains between the ten compounds, with rates ranging between 56 to 78% for the ten chemosensitizers. The use of DEAs in combination with quinoline seems to be thus a promising strategy for limiting the development of drug resistant strains and for treating patients in drug resistant areas.


Url:
DOI: 10.2174/157340608785700234


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Hal:pasteur-00590982

Le document en format XML

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<idno type="IdRef">15863621X</idno>
<idno type="ISNI">0000 0001 2176 4817</idno>
<orgName>Aix Marseille Université</orgName>
<orgName type="acronym">AMU</orgName>
<date type="start">2012-01-01</date>
<desc>
<address>
<addrLine>Aix-Marseille UniversitéJardins du Pharo58 Boulevard Charles Livon13284 Marseille cedex 7</addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://www.univ-amu.fr/</ref>
</desc>
</org>
</tutelle>
<tutelle name="UMR_MD1" active="#struct-303623" type="direct">
<org type="institution" xml:id="struct-303623" status="VALID">
<idno type="IdRef">026388278</idno>
<orgName>Institut National de la Santé et de la Recherche Médicale</orgName>
<orgName type="acronym">INSERM</orgName>
<desc>
<address>
<addrLine>101, rue de Tolbiac, 75013 Paris </addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://www.inserm.fr</ref>
</desc>
</org>
</tutelle>
</tutelles>
</hal:affiliation>
<country>France</country>
<placeName>
<settlement type="city">Marseille</settlement>
<region type="region" nuts="2">Provence-Alpes-Côte d'Azur</region>
</placeName>
<orgName type="university">Université d'Aix-Marseille</orgName>
</affiliation>
</author>
<author>
<name sortKey="Pradines, Bruno" sort="Pradines, Bruno" uniqKey="Pradines B" first="Bruno" last="Pradines">Bruno Pradines</name>
<affiliation wicri:level="1">
<hal:affiliation type="laboratory" xml:id="struct-127922" status="OLD">
<orgName>Unité de Recherche en Biologie et Epidémiologie Parasitaires</orgName>
<desc>
<address>
<addrLine>UMR6236-IFR48, Institut de Médecine Tropicale du Service de Santé des Armées (IMTSSA), Marseille, France</addrLine>
<country key="FR"></country>
</address>
</desc>
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<tutelle active="#struct-307023" type="direct">
<org type="institution" xml:id="struct-307023" status="INCOMING">
<orgName>Institut de Médecine Tropicale du Service de Santé des Armées</orgName>
<desc>
<address>
<country key="FR"></country>
</address>
</desc>
</org>
</tutelle>
<tutelle name="UMR6236" 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>
<country>France</country>
</affiliation>
</author>
</analytic>
<idno type="DOI">10.2174/157340608785700234</idno>
<series>
<title level="j">Medicinal Chemistry</title>
<idno type="ISSN">1573-4064</idno>
<imprint>
<date type="datePub">2008-09</date>
</imprint>
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<profileDesc>
<textClass>
<keywords scheme="mix" xml:lang="en">
<term>Malaria</term>
<term>antimalarial drug</term>
<term>chemosensitizer</term>
<term>quinoline resistance</term>
<term>reversal agent</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<p>The capacity of ten molecules for reversing resistance in Plasmodium falciparum in vitro to quinoline antimalarial drugs, such as chloroquine (CQ), quinine (QN), mefloquine (MQ) and monodesethylamodiaquine (MDAQ), was assessed against 27 Plasmodium falciparum isolates. Four of these compounds were 9,10-dihydroethanoanthracene derivatives (DEAs). These DEAs reversed 75 to 92% of the CQ resistant strains. These synthetic compounds were more effective in combination with CQ than verapamil, ketotifen, chlorpromazine, reserpine or nicardipine, which reversed less than 50% of the CQ resistant strains. DEAs significantly reversed 67 to 100% of MDAQ resistant parasites. These compounds were more effective in combination with MDAQ than ketotifen (60% of reversal), chlorpromazine (45%), verapamil (33%), reserpine (30%) or nicardipine (9%). The reversal activity of MQ resistance was less pronounced, regardless of the molecule tested, and was homogeneous with a rate ranging from 42% for ketotifen to 58% for reserpine, nicardipine, verapamil and cyproheptadine. The four DEAs significantly reversed 50 to 55% of the parasites resistant to MQ. Fifty-six to 78 % of the QN resistant parasites were reversed by the synthetic DEAs. There were few differences in the rate of reversal activity on QN resistant strains between the ten compounds, with rates ranging between 56 to 78% for the ten chemosensitizers. The use of DEAs in combination with quinoline seems to be thus a promising strategy for limiting the development of drug resistant strains and for treating patients in drug resistant areas.</p>
</div>
</front>
</TEI>
<affiliations>
<list>
<country>
<li>France</li>
</country>
<region>
<li>Provence-Alpes-Côte d'Azur</li>
</region>
<settlement>
<li>Marseille</li>
</settlement>
<orgName>
<li>Université d'Aix-Marseille</li>
</orgName>
</list>
<tree>
<noCountry>
<name sortKey="Legrand, Eric" sort="Legrand, Eric" uniqKey="Legrand E" first="Eric" last="Legrand">Eric Legrand</name>
</noCountry>
<country name="France">
<noRegion>
<name sortKey="Henry, Maud" sort="Henry, Maud" uniqKey="Henry M" first="Maud" last="Henry">Maud Henry</name>
</noRegion>
<name sortKey="Alibert, Sandrine" sort="Alibert, Sandrine" uniqKey="Alibert S" first="Sandrine" last="Alibert">Sandrine Alibert</name>
<name sortKey="Amalvict, Remy" sort="Amalvict, Remy" uniqKey="Amalvict R" first="Rémy" last="Amalvict">Rémy Amalvict</name>
<name sortKey="Baragatti, Meili" sort="Baragatti, Meili" uniqKey="Baragatti M" first="Meili" last="Baragatti">Meili Baragatti</name>
<name sortKey="Barbe, Jacques" sort="Barbe, Jacques" uniqKey="Barbe J" first="Jacques" last="Barbe">Jacques Barbe</name>
<name sortKey="Baret, Eric" sort="Baret, Eric" uniqKey="Baret E" first="Eric" last="Baret">Eric Baret</name>
<name sortKey="Fusai, Thierry" sort="Fusai, Thierry" uniqKey="Fusai T" first="Thierry" last="Fusai">Thierry Fusai</name>
<name sortKey="Mosnier, Joel" sort="Mosnier, Joel" uniqKey="Mosnier J" first="Joel" last="Mosnier">Joel Mosnier</name>
<name sortKey="Pages, Jean Marie" sort="Pages, Jean Marie" uniqKey="Pages J" first="Jean-Marie" last="Pagès">Jean-Marie Pagès</name>
<name sortKey="Pradines, Bruno" sort="Pradines, Bruno" uniqKey="Pradines B" first="Bruno" last="Pradines">Bruno Pradines</name>
<name sortKey="Rogier, Christophe" sort="Rogier, Christophe" uniqKey="Rogier C" first="Christophe" last="Rogier">Christophe Rogier</name>
</country>
</tree>
</affiliations>
</record>

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