Synthesis and antimalarial activity of new amino analogues of amodiaquine.
Identifieur interne : 000216 ( Hal/Checkpoint ); précédent : 000215; suivant : 000217Synthesis and antimalarial activity of new amino analogues of amodiaquine.
Auteurs : E. Paunescu [France] ; Sophie Susplugas [France] ; E. Boll ; R. Varga ; Elisabeth Mouray [France] ; Philippe Grellier [France] ; Patricia Melnyk [France]Source :
- Medicinal Chemistry [ 1573-4064 ] ; 2008.
Abstract
Amodiaquine remains one of the most prescribed antimalarial 4-aminoquinoline. To assess the importance of the 4'-hydroxyl group and subsequent hydrogen bond in the antimalarial activity of amodiaquine (AQ), a series of new analogues in which this functionality was replaced by various amino groups was synthesized. The incorporation of a 3'-pyrrolidinamino group instead of the 3'-diethylamino function of AQ allowed the development of a parallel series of amopyroquine derivatives. The compounds were screened against both chloroquine (CQ)-sensitive and -resistant strains of Plasmodium falciparum and their cytotoxicity evaluated upon the MRC5 cell line. Antimalarial activity in a low nanomolar range was recorded showing that the 4'-hydroxy function can be successfully replaced by various amino substituents in terms of activity without any influence of the level of CQ-resistance of the strains. Furthermore the ability of the compounds to inhibit beta-hematin formation was measured in order to discuss the mechanism of action of these new compounds. Compounds 7d and 8d exhibit a high selectivity index and may be considered as promising leads for further development.
Url:
DOI: 10.2174/157340608785700153
Links toward previous steps (curation, corpus...)
Links to Exploration step
Hal:mnhn-02070086Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Synthesis and antimalarial activity of new amino analogues of amodiaquine.</title><author><name sortKey="Paunescu, E" sort="Paunescu, E" uniqKey="Paunescu E" first="E" last="Paunescu">E. Paunescu</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-24511" status="OLD"> <orgName>Institut de biologie de Lille - IBL</orgName> <orgName type="acronym">IBLI</orgName> <desc> <address> <addrLine>Institut de Biologie de Lille 1 Rue du Professeur Calmette - 447 59021 LILLE CEDEX</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.ibl.fr</ref> </desc> <listRelation> <relation active="#struct-92973" type="direct"></relation> <relation active="#struct-300166" type="direct"></relation> <relation active="#struct-301247" type="indirect"></relation> <relation name="UMR8161" active="#struct-441569" type="direct"></relation> <relation active="#struct-361611" type="direct"></relation> </listRelation> <tutelles><tutelle active="#struct-92973" type="direct"><org type="institution" xml:id="struct-92973" status="OLD"> <idno type="IdRef">026404184</idno> <orgName>Université de Lille, Sciences et Technologies</orgName> <date type="end">2017-12-31</date> <desc> <address> <addrLine>Cité Scientifique - 59655 Villeneuve d'Ascq Cedex</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.univ-lille1.fr/</ref> </desc> </org></tutelle><tutelle active="#struct-300166" type="direct"><org type="institution" xml:id="struct-300166" status="VALID"> <orgName>Institut Pasteur de Lille</orgName> <date type="start">1894</date> <desc> <address> <addrLine>1 Rue du Professeur Calmette - Lille Cedex - 59019</addrLine> <country key="FR"></country> </address> <ref type="url">https://www.pasteur-lille.fr/accueil/</ref> </desc> <listRelation> <relation active="#struct-301247" type="direct"></relation> </listRelation> </org></tutelle><tutelle active="#struct-301247" type="indirect"><org type="regroupinstitution" xml:id="struct-301247" status="VALID"> <orgName>Réseau International des Instituts Pasteur</orgName> <orgName type="acronym">RIIP</orgName> <desc> <address> <addrLine>25, rue du Dr Roux 75724 Paris Cedex 15</addrLine> <country key="FR"></country> </address> <ref type="url">https://research.pasteur.fr/ip-network</ref> </desc> </org></tutelle><tutelle name="UMR8161" 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><tutelle active="#struct-361611" type="direct"><org type="institution" xml:id="struct-361611" status="OLD"> <idno type="ISNI">0000000120977060</idno> <idno type="IdRef">026404389</idno> <orgName>Université de Lille, Droit et Santé</orgName> <date type="end">2017-12-31</date> <desc> <address> <addrLine>42 rue Paul Duez 59000 Lille</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.univ-lille2.fr/</ref> </desc> </org></tutelle></tutelles></hal:affiliation><country>France</country></affiliation></author><author><name sortKey="Susplugas, Sophie" sort="Susplugas, Sophie" uniqKey="Susplugas S" first="Sophie" last="Susplugas">Sophie Susplugas</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-497906" status="VALID"> <orgName>Molécules de Communication et Adaptation des Micro-organismes</orgName> <orgName type="acronym">MCAM</orgName> <desc> <address> <addrLine>57 rue Cuvier - 75005 Paris</addrLine> <country key="FR"></country> </address> </desc> <listRelation> <relation active="#struct-7512" type="direct"></relation> <relation name="UMR 7245" active="#struct-441569" type="direct"></relation> </listRelation> <tutelles><tutelle active="#struct-7512" type="direct"><org type="institution" xml:id="struct-7512" status="VALID"> <orgName>Muséum national d'Histoire naturelle</orgName> <orgName type="acronym">MNHN</orgName> <desc> <address> <addrLine>57, rue Cuvier - 75231 Paris Cedex 05</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.mnhn.fr</ref> </desc> </org></tutelle><tutelle name="UMR 7245" 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="Boll, E" sort="Boll, E" uniqKey="Boll E" first="E" last="Boll">E. Boll</name></author><author><name sortKey="Varga, R" sort="Varga, R" uniqKey="Varga R" first="R" last="Varga">R. Varga</name></author><author><name sortKey="Mouray, Elisabeth" sort="Mouray, Elisabeth" uniqKey="Mouray E" first="Elisabeth" last="Mouray">Elisabeth Mouray</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-497906" status="VALID"> <orgName>Molécules de Communication et Adaptation des Micro-organismes</orgName> <orgName type="acronym">MCAM</orgName> <desc> <address> <addrLine>57 rue Cuvier - 75005 Paris</addrLine> <country key="FR"></country> </address> </desc> <listRelation> <relation active="#struct-7512" type="direct"></relation> <relation name="UMR 7245" active="#struct-441569" type="direct"></relation> </listRelation> <tutelles><tutelle active="#struct-7512" type="direct"><org type="institution" xml:id="struct-7512" status="VALID"> <orgName>Muséum national d'Histoire naturelle</orgName> <orgName type="acronym">MNHN</orgName> <desc> <address> <addrLine>57, rue Cuvier - 75231 Paris Cedex 05</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.mnhn.fr</ref> </desc> </org></tutelle><tutelle name="UMR 7245" 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="Grellier, Philippe" sort="Grellier, Philippe" uniqKey="Grellier P" first="Philippe" last="Grellier">Philippe Grellier</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-497906" status="VALID"> <orgName>Molécules de Communication et Adaptation des Micro-organismes</orgName> <orgName type="acronym">MCAM</orgName> <desc> <address> <addrLine>57 rue Cuvier - 75005 Paris</addrLine> <country key="FR"></country> </address> </desc> <listRelation> <relation active="#struct-7512" type="direct"></relation> <relation name="UMR 7245" active="#struct-441569" type="direct"></relation> </listRelation> <tutelles><tutelle active="#struct-7512" type="direct"><org type="institution" xml:id="struct-7512" status="VALID"> <orgName>Muséum national d'Histoire naturelle</orgName> <orgName type="acronym">MNHN</orgName> <desc> <address> <addrLine>57, rue Cuvier - 75231 Paris Cedex 05</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.mnhn.fr</ref> </desc> </org></tutelle><tutelle name="UMR 7245" 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="Melnyk, Patricia" sort="Melnyk, Patricia" uniqKey="Melnyk P" first="Patricia" last="Melnyk">Patricia Melnyk</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-24511" status="OLD"> <orgName>Institut de biologie de Lille - IBL</orgName> <orgName type="acronym">IBLI</orgName> <desc> <address> <addrLine>Institut de Biologie de Lille 1 Rue du Professeur Calmette - 447 59021 LILLE CEDEX</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.ibl.fr</ref> </desc> <listRelation> <relation active="#struct-92973" type="direct"></relation> <relation active="#struct-300166" type="direct"></relation> <relation active="#struct-301247" type="indirect"></relation> <relation name="UMR8161" active="#struct-441569" type="direct"></relation> <relation active="#struct-361611" type="direct"></relation> </listRelation> <tutelles><tutelle active="#struct-92973" type="direct"><org type="institution" xml:id="struct-92973" status="OLD"> <idno type="IdRef">026404184</idno> <orgName>Université de Lille, Sciences et Technologies</orgName> <date type="end">2017-12-31</date> <desc> <address> <addrLine>Cité Scientifique - 59655 Villeneuve d'Ascq Cedex</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.univ-lille1.fr/</ref> </desc> </org></tutelle><tutelle active="#struct-300166" type="direct"><org type="institution" xml:id="struct-300166" status="VALID"> <orgName>Institut Pasteur de Lille</orgName> <date type="start">1894</date> <desc> <address> <addrLine>1 Rue du Professeur Calmette - Lille Cedex - 59019</addrLine> <country key="FR"></country> </address> <ref type="url">https://www.pasteur-lille.fr/accueil/</ref> </desc> <listRelation> <relation active="#struct-301247" type="direct"></relation> </listRelation> </org></tutelle><tutelle active="#struct-301247" type="indirect"><org type="regroupinstitution" xml:id="struct-301247" status="VALID"> <orgName>Réseau International des Instituts Pasteur</orgName> <orgName type="acronym">RIIP</orgName> <desc> <address> <addrLine>25, rue du Dr Roux 75724 Paris Cedex 15</addrLine> <country key="FR"></country> </address> <ref type="url">https://research.pasteur.fr/ip-network</ref> </desc> </org></tutelle><tutelle name="UMR8161" 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><tutelle active="#struct-361611" type="direct"><org type="institution" xml:id="struct-361611" status="OLD"> <idno type="ISNI">0000000120977060</idno> <idno type="IdRef">026404389</idno> <orgName>Université de Lille, Droit et Santé</orgName> <date type="end">2017-12-31</date> <desc> <address> <addrLine>42 rue Paul Duez 59000 Lille</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.univ-lille2.fr/</ref> </desc> </org></tutelle></tutelles></hal:affiliation><country>France</country></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">HAL</idno><idno type="RBID">Hal:mnhn-02070086</idno><idno type="halId">mnhn-02070086</idno><idno type="halUri">https://hal-mnhn.archives-ouvertes.fr/mnhn-02070086</idno><idno type="url">https://hal-mnhn.archives-ouvertes.fr/mnhn-02070086</idno><idno type="doi">10.2174/157340608785700153</idno><date when="2008">2008</date><idno type="wicri:Area/Hal/Corpus">000223</idno><idno type="wicri:Area/Hal/Curation">000223</idno><idno type="wicri:Area/Hal/Checkpoint">000216</idno><idno type="wicri:explorRef" wicri:stream="Hal" wicri:step="Checkpoint">000216</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Synthesis and antimalarial activity of new amino analogues of amodiaquine.</title><author><name sortKey="Paunescu, E" sort="Paunescu, E" uniqKey="Paunescu E" first="E" last="Paunescu">E. Paunescu</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-24511" status="OLD"> <orgName>Institut de biologie de Lille - IBL</orgName> <orgName type="acronym">IBLI</orgName> <desc> <address> <addrLine>Institut de Biologie de Lille 1 Rue du Professeur Calmette - 447 59021 LILLE CEDEX</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.ibl.fr</ref> </desc> <listRelation> <relation active="#struct-92973" type="direct"></relation> <relation active="#struct-300166" type="direct"></relation> <relation active="#struct-301247" type="indirect"></relation> <relation name="UMR8161" active="#struct-441569" type="direct"></relation> <relation active="#struct-361611" type="direct"></relation> </listRelation> <tutelles><tutelle active="#struct-92973" type="direct"><org type="institution" xml:id="struct-92973" status="OLD"> <idno type="IdRef">026404184</idno> <orgName>Université de Lille, Sciences et Technologies</orgName> <date type="end">2017-12-31</date> <desc> <address> <addrLine>Cité Scientifique - 59655 Villeneuve d'Ascq Cedex</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.univ-lille1.fr/</ref> </desc> </org></tutelle><tutelle active="#struct-300166" type="direct"><org type="institution" xml:id="struct-300166" status="VALID"> <orgName>Institut Pasteur de Lille</orgName> <date type="start">1894</date> <desc> <address> <addrLine>1 Rue du Professeur Calmette - Lille Cedex - 59019</addrLine> <country key="FR"></country> </address> <ref type="url">https://www.pasteur-lille.fr/accueil/</ref> </desc> <listRelation> <relation active="#struct-301247" type="direct"></relation> </listRelation> </org></tutelle><tutelle active="#struct-301247" type="indirect"><org type="regroupinstitution" xml:id="struct-301247" status="VALID"> <orgName>Réseau International des Instituts Pasteur</orgName> <orgName type="acronym">RIIP</orgName> <desc> <address> <addrLine>25, rue du Dr Roux 75724 Paris Cedex 15</addrLine> <country key="FR"></country> </address> <ref type="url">https://research.pasteur.fr/ip-network</ref> </desc> </org></tutelle><tutelle name="UMR8161" 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><tutelle active="#struct-361611" type="direct"><org type="institution" xml:id="struct-361611" status="OLD"> <idno type="ISNI">0000000120977060</idno> <idno type="IdRef">026404389</idno> <orgName>Université de Lille, Droit et Santé</orgName> <date type="end">2017-12-31</date> <desc> <address> <addrLine>42 rue Paul Duez 59000 Lille</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.univ-lille2.fr/</ref> </desc> </org></tutelle></tutelles></hal:affiliation><country>France</country></affiliation></author><author><name sortKey="Susplugas, Sophie" sort="Susplugas, Sophie" uniqKey="Susplugas S" first="Sophie" last="Susplugas">Sophie Susplugas</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-497906" status="VALID"> <orgName>Molécules de Communication et Adaptation des Micro-organismes</orgName> <orgName type="acronym">MCAM</orgName> <desc> <address> <addrLine>57 rue Cuvier - 75005 Paris</addrLine> <country key="FR"></country> </address> </desc> <listRelation> <relation active="#struct-7512" type="direct"></relation> <relation name="UMR 7245" active="#struct-441569" type="direct"></relation> </listRelation> <tutelles><tutelle active="#struct-7512" type="direct"><org type="institution" xml:id="struct-7512" status="VALID"> <orgName>Muséum national d'Histoire naturelle</orgName> <orgName type="acronym">MNHN</orgName> <desc> <address> <addrLine>57, rue Cuvier - 75231 Paris Cedex 05</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.mnhn.fr</ref> </desc> </org></tutelle><tutelle name="UMR 7245" 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="Boll, E" sort="Boll, E" uniqKey="Boll E" first="E" last="Boll">E. Boll</name></author><author><name sortKey="Varga, R" sort="Varga, R" uniqKey="Varga R" first="R" last="Varga">R. Varga</name></author><author><name sortKey="Mouray, Elisabeth" sort="Mouray, Elisabeth" uniqKey="Mouray E" first="Elisabeth" last="Mouray">Elisabeth Mouray</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-497906" status="VALID"> <orgName>Molécules de Communication et Adaptation des Micro-organismes</orgName> <orgName type="acronym">MCAM</orgName> <desc> <address> <addrLine>57 rue Cuvier - 75005 Paris</addrLine> <country key="FR"></country> </address> </desc> <listRelation> <relation active="#struct-7512" type="direct"></relation> <relation name="UMR 7245" active="#struct-441569" type="direct"></relation> </listRelation> <tutelles><tutelle active="#struct-7512" type="direct"><org type="institution" xml:id="struct-7512" status="VALID"> <orgName>Muséum national d'Histoire naturelle</orgName> <orgName type="acronym">MNHN</orgName> <desc> <address> <addrLine>57, rue Cuvier - 75231 Paris Cedex 05</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.mnhn.fr</ref> </desc> </org></tutelle><tutelle name="UMR 7245" 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="Grellier, Philippe" sort="Grellier, Philippe" uniqKey="Grellier P" first="Philippe" last="Grellier">Philippe Grellier</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-497906" status="VALID"> <orgName>Molécules de Communication et Adaptation des Micro-organismes</orgName> <orgName type="acronym">MCAM</orgName> <desc> <address> <addrLine>57 rue Cuvier - 75005 Paris</addrLine> <country key="FR"></country> </address> </desc> <listRelation> <relation active="#struct-7512" type="direct"></relation> <relation name="UMR 7245" active="#struct-441569" type="direct"></relation> </listRelation> <tutelles><tutelle active="#struct-7512" type="direct"><org type="institution" xml:id="struct-7512" status="VALID"> <orgName>Muséum national d'Histoire naturelle</orgName> <orgName type="acronym">MNHN</orgName> <desc> <address> <addrLine>57, rue Cuvier - 75231 Paris Cedex 05</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.mnhn.fr</ref> </desc> </org></tutelle><tutelle name="UMR 7245" 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="Melnyk, Patricia" sort="Melnyk, Patricia" uniqKey="Melnyk P" first="Patricia" last="Melnyk">Patricia Melnyk</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-24511" status="OLD"> <orgName>Institut de biologie de Lille - IBL</orgName> <orgName type="acronym">IBLI</orgName> <desc> <address> <addrLine>Institut de Biologie de Lille 1 Rue du Professeur Calmette - 447 59021 LILLE CEDEX</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.ibl.fr</ref> </desc> <listRelation> <relation active="#struct-92973" type="direct"></relation> <relation active="#struct-300166" type="direct"></relation> <relation active="#struct-301247" type="indirect"></relation> <relation name="UMR8161" active="#struct-441569" type="direct"></relation> <relation active="#struct-361611" type="direct"></relation> </listRelation> <tutelles><tutelle active="#struct-92973" type="direct"><org type="institution" xml:id="struct-92973" status="OLD"> <idno type="IdRef">026404184</idno> <orgName>Université de Lille, Sciences et Technologies</orgName> <date type="end">2017-12-31</date> <desc> <address> <addrLine>Cité Scientifique - 59655 Villeneuve d'Ascq Cedex</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.univ-lille1.fr/</ref> </desc> </org></tutelle><tutelle active="#struct-300166" type="direct"><org type="institution" xml:id="struct-300166" status="VALID"> <orgName>Institut Pasteur de Lille</orgName> <date type="start">1894</date> <desc> <address> <addrLine>1 Rue du Professeur Calmette - Lille Cedex - 59019</addrLine> <country key="FR"></country> </address> <ref type="url">https://www.pasteur-lille.fr/accueil/</ref> </desc> <listRelation> <relation active="#struct-301247" type="direct"></relation> </listRelation> </org></tutelle><tutelle active="#struct-301247" type="indirect"><org type="regroupinstitution" xml:id="struct-301247" status="VALID"> <orgName>Réseau International des Instituts Pasteur</orgName> <orgName type="acronym">RIIP</orgName> <desc> <address> <addrLine>25, rue du Dr Roux 75724 Paris Cedex 15</addrLine> <country key="FR"></country> </address> <ref type="url">https://research.pasteur.fr/ip-network</ref> </desc> </org></tutelle><tutelle name="UMR8161" 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><tutelle active="#struct-361611" type="direct"><org type="institution" xml:id="struct-361611" status="OLD"> <idno type="ISNI">0000000120977060</idno> <idno type="IdRef">026404389</idno> <orgName>Université de Lille, Droit et Santé</orgName> <date type="end">2017-12-31</date> <desc> <address> <addrLine>42 rue Paul Duez 59000 Lille</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.univ-lille2.fr/</ref> </desc> </org></tutelle></tutelles></hal:affiliation><country>France</country></affiliation></author></analytic><idno type="DOI">10.2174/157340608785700153</idno><series><title level="j">Medicinal Chemistry</title><idno type="ISSN">1573-4064</idno><imprint><date type="datePub">2008</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"> <p>Amodiaquine remains one of the most prescribed antimalarial 4-aminoquinoline. To assess the importance of the 4'-hydroxyl group and subsequent hydrogen bond in the antimalarial activity of amodiaquine (AQ), a series of new analogues in which this functionality was replaced by various amino groups was synthesized. The incorporation of a 3'-pyrrolidinamino group instead of the 3'-diethylamino function of AQ allowed the development of a parallel series of amopyroquine derivatives. The compounds were screened against both chloroquine (CQ)-sensitive and -resistant strains of Plasmodium falciparum and their cytotoxicity evaluated upon the MRC5 cell line. Antimalarial activity in a low nanomolar range was recorded showing that the 4'-hydroxy function can be successfully replaced by various amino substituents in terms of activity without any influence of the level of CQ-resistance of the strains. Furthermore the ability of the compounds to inhibit beta-hematin formation was measured in order to discuss the mechanism of action of these new compounds. Compounds 7d and 8d exhibit a high selectivity index and may be considered as promising leads for further development.</p> </div></front></TEI><hal api="V3"> <titleStmt> <title xml:lang="en">Synthesis and antimalarial activity of new amino analogues of amodiaquine.</title> <author role="aut"> <persName> <forename type="first">E</forename> <surname>Paunescu</surname> </persName> <idno type="halauthorid">11437270</idno> <affiliation ref="#struct-24511"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Sophie</forename> <surname>Susplugas</surname> </persName> <idno type="halauthorid">395277</idno> <affiliation ref="#struct-497906"></affiliation> </author> <author role="aut"> <persName> <forename type="first">E</forename> <surname>Boll</surname> </persName> <idno type="halauthorid">11437271</idno> </author> <author role="aut"> <persName> <forename type="first">R</forename> <forename type="middle">A</forename> <surname>Varga</surname> </persName> <idno type="halauthorid">11437280</idno> </author> <author role="aut"> <persName> <forename type="first">Elisabeth</forename> <surname>Mouray</surname> </persName> <idno type="halauthorid">318333</idno> <affiliation ref="#struct-497906"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Philippe</forename> <surname>Grellier</surname> </persName> <email type="md5">7daf39af4cc37fc73467e0a136dcba67</email> <email type="domain">mnhn.fr</email> <idno type="halauthorid">182251</idno> <affiliation ref="#struct-497906"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Patricia</forename> <surname>Melnyk</surname> </persName> <email type="md5">2dd96a706c78b363c89102444921b966</email> <email type="domain">univ-lille.fr</email> <idno type="idhal" notation="string">patricia-melnyk</idno> <idno type="idhal" notation="numeric">172378</idno> <idno type="halauthorid">128613</idno> <idno type="ORCID">https://orcid.org/0000-0002-9555-3446</idno> <affiliation ref="#struct-24511"></affiliation> </author> <editor role="depositor"> <persName> <forename>Philippe</forename> <surname>Grellier</surname> </persName> <email type="md5">0c0b49eab60379243604b1750068ef0b</email> <email type="domain">mnhn.fr</email> </editor> </titleStmt> <editionStmt> <edition n="v1" type="current"> <date type="whenSubmitted">2019-03-16 17:07:05</date> <date type="whenModified">2020-02-18 14:12:38</date> <date type="whenReleased">2019-03-16 17:07:05</date> <date type="whenProduced">2008</date> </edition> <respStmt> <resp>contributor</resp> <name key="481244"> <persName> <forename>Philippe</forename> <surname>Grellier</surname> </persName> <email type="md5">0c0b49eab60379243604b1750068ef0b</email> <email type="domain">mnhn.fr</email> </name> </respStmt> </editionStmt> <publicationStmt> <distributor>CCSD</distributor> <idno type="halId">mnhn-02070086</idno> <idno type="halUri">https://hal-mnhn.archives-ouvertes.fr/mnhn-02070086</idno> <idno type="halBibtex">paunescu:mnhn-02070086</idno> <idno type="halRefHtml">Medicinal Chemistry, Bentham Science Publishers, 2008, 4 (5), pp.405-427. ⟨10.2174/157340608785700153⟩</idno> <idno type="halRef">Medicinal Chemistry, Bentham Science Publishers, 2008, 4 (5), pp.405-427. ⟨10.2174/157340608785700153⟩</idno> </publicationStmt> <seriesStmt> <idno type="stamp" n="MNHN">Muséum National d'Histoire Naturelle</idno> <idno type="stamp" n="CNRS">CNRS - Centre national de la recherche scientifique</idno> <idno type="stamp" n="RIIP">Institut Pasteur RIIP (Réseau International)</idno> <idno type="stamp" n="RIIP_LILLE">Institut Pasteur de Lille</idno> </seriesStmt> <notesStmt> <note type="audience" n="2">International</note> <note type="popular" n="0">No</note> <note type="peer" n="1">Yes</note> </notesStmt> <sourceDesc> <biblStruct> <analytic> <title xml:lang="en">Synthesis and antimalarial activity of new amino analogues of amodiaquine.</title> <author role="aut"> <persName> <forename type="first">E</forename> <surname>Paunescu</surname> </persName> <idno type="halauthorid">11437270</idno> <affiliation ref="#struct-24511"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Sophie</forename> <surname>Susplugas</surname> </persName> <idno type="halauthorid">395277</idno> <affiliation ref="#struct-497906"></affiliation> </author> <author role="aut"> <persName> <forename type="first">E</forename> <surname>Boll</surname> </persName> <idno type="halauthorid">11437271</idno> </author> <author role="aut"> <persName> <forename type="first">R</forename> <forename type="middle">A</forename> <surname>Varga</surname> </persName> <idno type="halauthorid">11437280</idno> </author> <author role="aut"> <persName> <forename type="first">Elisabeth</forename> <surname>Mouray</surname> </persName> <idno type="halauthorid">318333</idno> <affiliation ref="#struct-497906"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Philippe</forename> <surname>Grellier</surname> </persName> <email type="md5">7daf39af4cc37fc73467e0a136dcba67</email> <email type="domain">mnhn.fr</email> <idno type="halauthorid">182251</idno> <affiliation ref="#struct-497906"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Patricia</forename> <surname>Melnyk</surname> </persName> <email type="md5">2dd96a706c78b363c89102444921b966</email> <email type="domain">univ-lille.fr</email> <idno type="idhal" notation="string">patricia-melnyk</idno> <idno type="idhal" notation="numeric">172378</idno> <idno type="halauthorid">128613</idno> <idno type="ORCID">https://orcid.org/0000-0002-9555-3446</idno> <affiliation ref="#struct-24511"></affiliation> </author> </analytic> <monogr> <idno type="halJournalId" status="VALID">17001</idno> <idno type="issn">1573-4064</idno> <title level="j">Medicinal Chemistry</title> <imprint> <publisher>Bentham Science Publishers</publisher> <biblScope unit="volume">4</biblScope> <biblScope unit="issue">5</biblScope> <biblScope unit="pp">405-427</biblScope> <date type="datePub">2008</date> </imprint> </monogr> <idno type="doi">10.2174/157340608785700153</idno> <idno type="pubmed">18782038</idno> </biblStruct> </sourceDesc> <profileDesc> <langUsage> <language ident="en">English</language> </langUsage> <textClass> <classCode scheme="mesh">Amines/chemistry*</classCode> <classCode scheme="mesh">Amodiaquine/analogs & derivatives</classCode> <classCode scheme="mesh">Plasmodium falciparum/drug effects*</classCode> <classCode scheme="mesh">Plasmodium falciparum/growth & development</classCode> <classCode scheme="mesh">Pyrrolidines/chemistry</classCode> <classCode scheme="mesh">Structure-Activity Relationship</classCode> <classCode scheme="mesh">Amodiaquine/chemical synthesis</classCode> <classCode scheme="mesh">Amodiaquine/pharmacology*</classCode> <classCode scheme="mesh">Animals</classCode> <classCode scheme="mesh">Antimalarials/chemical synthesis</classCode> <classCode scheme="mesh">Antimalarials/pharmacology*</classCode> <classCode scheme="mesh">Crystallography, X-Ray</classCode> <classCode scheme="mesh">Hydrogen Bonding</classCode> <classCode scheme="mesh">Models, Chemical</classCode> <classCode scheme="halDomain" n="chim">Chemical Sciences</classCode> <classCode scheme="halDomain" n="sdv">Life Sciences [q-bio]</classCode> <classCode scheme="halDomain" n="sdv.mp">Life Sciences [q-bio]/Microbiology and Parasitology</classCode> <classCode scheme="halTypology" n="ART">Journal articles</classCode> </textClass> <abstract xml:lang="en"> <p>Amodiaquine remains one of the most prescribed antimalarial 4-aminoquinoline. To assess the importance of the 4'-hydroxyl group and subsequent hydrogen bond in the antimalarial activity of amodiaquine (AQ), a series of new analogues in which this functionality was replaced by various amino groups was synthesized. The incorporation of a 3'-pyrrolidinamino group instead of the 3'-diethylamino function of AQ allowed the development of a parallel series of amopyroquine derivatives. The compounds were screened against both chloroquine (CQ)-sensitive and -resistant strains of Plasmodium falciparum and their cytotoxicity evaluated upon the MRC5 cell line. Antimalarial activity in a low nanomolar range was recorded showing that the 4'-hydroxy function can be successfully replaced by various amino substituents in terms of activity without any influence of the level of CQ-resistance of the strains. Furthermore the ability of the compounds to inhibit beta-hematin formation was measured in order to discuss the mechanism of action of these new compounds. Compounds 7d and 8d exhibit a high selectivity index and may be considered as promising leads for further development.</p> </abstract> </profileDesc> </hal></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/ChloroquineV1/Data/Hal/Checkpoint
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000216 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Hal/Checkpoint/biblio.hfd -nk 000216 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= ChloroquineV1
|flux= Hal
|étape= Checkpoint
|type= RBID
|clé= Hal:mnhn-02070086
|texte= Synthesis and antimalarial activity of new amino analogues of amodiaquine.
}}
| This area was generated with Dilib version V0.6.33. |  |