Synthesis and biological evaluation of acridine derivatives as antimalarial agents.
Identifieur interne : 000213 ( France/Analysis ); précédent : 000212; suivant : 000214Synthesis and biological evaluation of acridine derivatives as antimalarial agents.
Auteurs : Xiao-Min Yu ; Florence Ramiandrasoa ; Lucie Guetzoyan ; Bruno Pradines ; Edgar Quintino ; Daniele Gadelle ; Patrick Forterre ; Thierry Cresteil [France] ; Jean-Pierre Mahy ; Stéphanie PetheSource :
- ChemMedChem [ 1860-7179 ] ; 2012-04.
Abstract
New N-alkylaminoacridine derivatives attached to nitrogen heterocycles were synthesized, and their antimalarial potency was examined. They were tested in vitro against the growth of Plasmodium falciparum, including chloroquine (CQ)-susceptible and CQ-resistant strains. This biological evaluation has shown that the presence of a heterocyclic ring significantly increases the activity against P. falciparum. The best compound shows a nanomolar IC(50) value toward parasite proliferation on both CQ-susceptible and CQ-resistant strains. The antimalarial activity of these new acridine derivatives can be explained by the two mechanisms studied in this work. First, we showed the capacity of these compounds to inhibit heme biocrystallization, a detoxification process specific to the parasite and essential for its survival. Second, in our search for alternative targets, we evaluated the in vitro inhibitory activity of these compounds toward Sulfolobus shibatae topoisomerase VI-mediated DNA relaxation. The preliminary results obtained reveal that all tested compounds are potent DNA intercalators, and significantly inhibit the activity of S. shibatae topoisomerase VI at concentrations ranging between 2.0 and 2.5 μM.
Url:
DOI: 10.1002/cmdc.201100554
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream Hal, to step Corpus: 000224
- to stream Hal, to step Curation: 000224
- to stream Hal, to step Checkpoint: 000149
- to stream Main, to step Merge: 001280
- to stream Main, to step Curation: 001279
- to stream Main, to step Exploration: 001279
- to stream France, to step Extraction: 000213
Links to Exploration step
Hal:hal-00694423Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Synthesis and biological evaluation of acridine derivatives as antimalarial agents.</title>
<author><name sortKey="Yu, Xiao Min" sort="Yu, Xiao Min" uniqKey="Yu X" first="Xiao-Min" last="Yu">Xiao-Min Yu</name>
</author>
<author><name sortKey="Ramiandrasoa, Florence" sort="Ramiandrasoa, Florence" uniqKey="Ramiandrasoa F" first="Florence" last="Ramiandrasoa">Florence Ramiandrasoa</name>
</author>
<author><name sortKey="Guetzoyan, Lucie" sort="Guetzoyan, Lucie" uniqKey="Guetzoyan L" first="Lucie" last="Guetzoyan">Lucie Guetzoyan</name>
</author>
<author><name sortKey="Pradines, Bruno" sort="Pradines, Bruno" uniqKey="Pradines B" first="Bruno" last="Pradines">Bruno Pradines</name>
</author>
<author><name sortKey="Quintino, Edgar" sort="Quintino, Edgar" uniqKey="Quintino E" first="Edgar" last="Quintino">Edgar Quintino</name>
</author>
<author><name sortKey="Gadelle, Daniele" sort="Gadelle, Daniele" uniqKey="Gadelle D" first="Daniele" last="Gadelle">Daniele Gadelle</name>
</author>
<author><name sortKey="Forterre, Patrick" sort="Forterre, Patrick" uniqKey="Forterre P" first="Patrick" last="Forterre">Patrick Forterre</name>
</author>
<author><name sortKey="Cresteil, Thierry" sort="Cresteil, Thierry" uniqKey="Cresteil T" first="Thierry" last="Cresteil">Thierry Cresteil</name>
<affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-440" status="VALID"> <orgName>Institut de Chimie des Substances Naturelles</orgName>
<orgName type="acronym">ICSN</orgName>
<desc> <address> <addrLine>Avenue de la terrasse 91198 Gif sur yvette cedex</addrLine>
<country key="FR"></country>
</address>
</desc>
<listRelation> <relation name="UPR2301" active="#struct-441569" type="direct"></relation>
</listRelation>
<tutelles><tutelle name="UPR2301" 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>
<author><name sortKey="Mahy, Jean Pierre" sort="Mahy, Jean Pierre" uniqKey="Mahy J" first="Jean-Pierre" last="Mahy">Jean-Pierre Mahy</name>
</author>
<author><name sortKey="Pethe, Stephanie" sort="Pethe, Stephanie" uniqKey="Pethe S" first="Stéphanie" last="Pethe">Stéphanie Pethe</name>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">HAL</idno>
<idno type="RBID">Hal:hal-00694423</idno>
<idno type="halId">hal-00694423</idno>
<idno type="halUri">https://hal.archives-ouvertes.fr/hal-00694423</idno>
<idno type="url">https://hal.archives-ouvertes.fr/hal-00694423</idno>
<idno type="doi">10.1002/cmdc.201100554</idno>
<date when="2012-04">2012-04</date>
<idno type="wicri:Area/Hal/Corpus">000224</idno>
<idno type="wicri:Area/Hal/Curation">000224</idno>
<idno type="wicri:Area/Hal/Checkpoint">000149</idno>
<idno type="wicri:explorRef" wicri:stream="Hal" wicri:step="Checkpoint">000149</idno>
<idno type="wicri:doubleKey">1860-7179:2012:Yu X:synthesis:and:biological</idno>
<idno type="wicri:Area/Main/Merge">001280</idno>
<idno type="wicri:Area/Main/Curation">001279</idno>
<idno type="wicri:Area/Main/Exploration">001279</idno>
<idno type="wicri:Area/France/Extraction">000213</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en">Synthesis and biological evaluation of acridine derivatives as antimalarial agents.</title>
<author><name sortKey="Yu, Xiao Min" sort="Yu, Xiao Min" uniqKey="Yu X" first="Xiao-Min" last="Yu">Xiao-Min Yu</name>
</author>
<author><name sortKey="Ramiandrasoa, Florence" sort="Ramiandrasoa, Florence" uniqKey="Ramiandrasoa F" first="Florence" last="Ramiandrasoa">Florence Ramiandrasoa</name>
</author>
<author><name sortKey="Guetzoyan, Lucie" sort="Guetzoyan, Lucie" uniqKey="Guetzoyan L" first="Lucie" last="Guetzoyan">Lucie Guetzoyan</name>
</author>
<author><name sortKey="Pradines, Bruno" sort="Pradines, Bruno" uniqKey="Pradines B" first="Bruno" last="Pradines">Bruno Pradines</name>
</author>
<author><name sortKey="Quintino, Edgar" sort="Quintino, Edgar" uniqKey="Quintino E" first="Edgar" last="Quintino">Edgar Quintino</name>
</author>
<author><name sortKey="Gadelle, Daniele" sort="Gadelle, Daniele" uniqKey="Gadelle D" first="Daniele" last="Gadelle">Daniele Gadelle</name>
</author>
<author><name sortKey="Forterre, Patrick" sort="Forterre, Patrick" uniqKey="Forterre P" first="Patrick" last="Forterre">Patrick Forterre</name>
</author>
<author><name sortKey="Cresteil, Thierry" sort="Cresteil, Thierry" uniqKey="Cresteil T" first="Thierry" last="Cresteil">Thierry Cresteil</name>
<affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-440" status="VALID"> <orgName>Institut de Chimie des Substances Naturelles</orgName>
<orgName type="acronym">ICSN</orgName>
<desc> <address> <addrLine>Avenue de la terrasse 91198 Gif sur yvette cedex</addrLine>
<country key="FR"></country>
</address>
</desc>
<listRelation> <relation name="UPR2301" active="#struct-441569" type="direct"></relation>
</listRelation>
<tutelles><tutelle name="UPR2301" 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>
<author><name sortKey="Mahy, Jean Pierre" sort="Mahy, Jean Pierre" uniqKey="Mahy J" first="Jean-Pierre" last="Mahy">Jean-Pierre Mahy</name>
</author>
<author><name sortKey="Pethe, Stephanie" sort="Pethe, Stephanie" uniqKey="Pethe S" first="Stéphanie" last="Pethe">Stéphanie Pethe</name>
</author>
</analytic>
<idno type="DOI">10.1002/cmdc.201100554</idno>
<series><title level="j">ChemMedChem</title>
<idno type="ISSN">1860-7179</idno>
<imprint><date type="datePub">2012-04</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"> <p>New N-alkylaminoacridine derivatives attached to nitrogen heterocycles were synthesized, and their antimalarial potency was examined. They were tested in vitro against the growth of Plasmodium falciparum, including chloroquine (CQ)-susceptible and CQ-resistant strains. This biological evaluation has shown that the presence of a heterocyclic ring significantly increases the activity against P. falciparum. The best compound shows a nanomolar IC(50) value toward parasite proliferation on both CQ-susceptible and CQ-resistant strains. The antimalarial activity of these new acridine derivatives can be explained by the two mechanisms studied in this work. First, we showed the capacity of these compounds to inhibit heme biocrystallization, a detoxification process specific to the parasite and essential for its survival. Second, in our search for alternative targets, we evaluated the in vitro inhibitory activity of these compounds toward Sulfolobus shibatae topoisomerase VI-mediated DNA relaxation. The preliminary results obtained reveal that all tested compounds are potent DNA intercalators, and significantly inhibit the activity of S. shibatae topoisomerase VI at concentrations ranging between 2.0 and 2.5 μM.</p>
</div>
</front>
</TEI>
<affiliations><list><country><li>France</li>
</country>
</list>
<tree><noCountry><name sortKey="Forterre, Patrick" sort="Forterre, Patrick" uniqKey="Forterre P" first="Patrick" last="Forterre">Patrick Forterre</name>
<name sortKey="Gadelle, Daniele" sort="Gadelle, Daniele" uniqKey="Gadelle D" first="Daniele" last="Gadelle">Daniele Gadelle</name>
<name sortKey="Guetzoyan, Lucie" sort="Guetzoyan, Lucie" uniqKey="Guetzoyan L" first="Lucie" last="Guetzoyan">Lucie Guetzoyan</name>
<name sortKey="Mahy, Jean Pierre" sort="Mahy, Jean Pierre" uniqKey="Mahy J" first="Jean-Pierre" last="Mahy">Jean-Pierre Mahy</name>
<name sortKey="Pethe, Stephanie" sort="Pethe, Stephanie" uniqKey="Pethe S" first="Stéphanie" last="Pethe">Stéphanie Pethe</name>
<name sortKey="Pradines, Bruno" sort="Pradines, Bruno" uniqKey="Pradines B" first="Bruno" last="Pradines">Bruno Pradines</name>
<name sortKey="Quintino, Edgar" sort="Quintino, Edgar" uniqKey="Quintino E" first="Edgar" last="Quintino">Edgar Quintino</name>
<name sortKey="Ramiandrasoa, Florence" sort="Ramiandrasoa, Florence" uniqKey="Ramiandrasoa F" first="Florence" last="Ramiandrasoa">Florence Ramiandrasoa</name>
<name sortKey="Yu, Xiao Min" sort="Yu, Xiao Min" uniqKey="Yu X" first="Xiao-Min" last="Yu">Xiao-Min Yu</name>
</noCountry>
<country name="France"><noRegion><name sortKey="Cresteil, Thierry" sort="Cresteil, Thierry" uniqKey="Cresteil T" first="Thierry" last="Cresteil">Thierry Cresteil</name>
</noRegion>
</country>
</tree>
</affiliations>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/ChloroquineV1/Data/France/Analysis
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000213 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/France/Analysis/biblio.hfd -nk 000213 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Sante |area= ChloroquineV1 |flux= France |étape= Analysis |type= RBID |clé= Hal:hal-00694423 |texte= Synthesis and biological evaluation of acridine derivatives as antimalarial agents. }}
This area was generated with Dilib version V0.6.33. |