Parallel Solution-Phase Synthesis of Conformationally Restricted Congeners of Pentamidine and Evaluation of Their Antiplasmodial Activities
Identifieur interne : 001F20 ( Main/Exploration ); précédent : 001F19; suivant : 001F21Parallel Solution-Phase Synthesis of Conformationally Restricted Congeners of Pentamidine and Evaluation of Their Antiplasmodial Activities
Auteurs : Annie Mayence [États-Unis] ; Jean Jacques Vanden Eynde [États-Unis] ; Fran M. Krogstad [États-Unis] ; Donald J. Krogstad [États-Unis] ; Melanie T. Cushion [États-Unis] ; Tien L. Huang [États-Unis]Source :
- Journal of Medicinal Chemistry [ 0022-2623 ] ; 2004.
Descripteurs français
- KwdFr :
- Animaux, Antipaludiques (), Antipaludiques (pharmacologie), Antipaludiques (synthèse chimique), Chloroquine (pharmacologie), Conformation moléculaire, Humains, Hémine (métabolisme), Lignée cellulaire tumorale, Plasmodium falciparum (), Relation structure-activité, Résistance aux substances, Système acellulaire.
- MESH :
- métabolisme : Hémine.
- pharmacologie : Antipaludiques, Chloroquine.
- synthèse chimique : Antipaludiques.
- Animaux, Antipaludiques, Conformation moléculaire, Humains, Lignée cellulaire tumorale, Plasmodium falciparum, Relation structure-activité, Résistance aux substances, Système acellulaire.
- Pascal (Inist)
- Amidine, Antipaludique, Antiparasitaire, Antiprotozoaire, Benzamidine dérivé, Chimie combinatoire, Cytotoxicité, Encombrement stérique, Homme, Hétérocycle azote, In vitro, Lignée A549, Lignée cellulaire, Pentamidine, Phase liquide, Pipérazine dérivé, Pipérazine(1,4-bis[4-(1-alkylamidino)phényl]), Plasmodium falciparum, Poumon, Relation structure activité, Rigidité moléculaire, Synthèse chimique.
- Wicri :
- topic : Homme.
English descriptors
- KwdEn :
- Amidine, Animals, Antimalarial, Antimalarials (chemical synthesis), Antimalarials (chemistry), Antimalarials (pharmacology), Antiprotozoal agent, Cell Line, Tumor, Cell line, Cell-Free System, Chemical synthesis, Chloroquine (pharmacology), Combinatorial chemistry, Cytotoxicity, Drug Resistance, Hemin (metabolism), Human, Humans, In vitro, Liquid phase, Lung, Molecular Conformation, Molecular rigidity, Nitrogen heterocycle, Parasiticide, Pentamidine, Piperazine derivatives, Plasmodium falciparum, Plasmodium falciparum (drug effects), Steric hindrance, Structure activity relation, Structure-Activity Relationship.
- MESH :
- chemical , chemical synthesis : Antimalarials.
- chemical , chemistry : Antimalarials.
- chemical , metabolism : Hemin.
- chemical , pharmacology : Antimalarials, Chloroquine.
- drug effects : Plasmodium falciparum.
- Animals, Cell Line, Tumor, Cell-Free System, Drug Resistance, Humans, Molecular Conformation, Structure-Activity Relationship.
Abstract
Conformationally restricted bisbenzamidines and related congeners have been synthesized and evaluated for activity against two Plasmodium falciparum strains. The most active compounds, bisbenzamidines linked by a 1,4-piperazinediyl core, had IC50 values between 3 and 18 nM against both chloroquine-susceptible and -resistant parasites and IC50 values for cytotoxicity greater than 5 μM, using the A549 human lung epithelial cell line. DNA binding affinity, as estimated by ΔTm, did not correlate with either antiparasite effects or cytotoxicity. Each of the active bisbenzamidines interfered with the formation of hemozoin in cell-free systems.
Url:
DOI: 10.1021/jm030545e
Affiliations:
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Le document en format XML
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Pentamidine and Evaluation of Their Antiplasmodial Activities</title><author><name sortKey="Mayence, Annie" sort="Mayence, Annie" uniqKey="Mayence A" first="Annie" last="Mayence">Annie Mayence</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Ohio</region></placeName><wicri:cityArea>College of Pharmacy, Division of Basic Pharmaceutical Sciences, Xavier University of Louisiana, 1 Drexel Drive,New Orleans, Louisiana 70125, Departments of Tropical Medicine and Medicine, Center for Infectious Diseases,Tulane University, 1430 Tulane Avenue, New Orleans, Louisiana 70112, and Department of Internal Medicine,Division of Infectious Diseases, College of Medicine, University of Cincinnati, Cincinnati</wicri:cityArea></affiliation><affiliation></affiliation></author><author><name sortKey="Vanden Eynde, Jean Jacques" sort="Vanden Eynde, Jean Jacques" uniqKey="Vanden Eynde J" first="Jean Jacques" last="Vanden Eynde">Jean Jacques Vanden Eynde</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Ohio</region></placeName><wicri:cityArea>College of Pharmacy, Division of Basic Pharmaceutical Sciences, Xavier University of Louisiana, 1 Drexel Drive,New Orleans, Louisiana 70125, Departments of Tropical Medicine and Medicine, Center for Infectious Diseases,Tulane University, 1430 Tulane Avenue, New Orleans, Louisiana 70112, and Department of Internal Medicine,Division of Infectious Diseases, College of Medicine, University of Cincinnati, Cincinnati</wicri:cityArea></affiliation><affiliation></affiliation></author><author><name sortKey="Krogstad, Fran M" sort="Krogstad, Fran M" uniqKey="Krogstad F" first="Fran M." last="Krogstad">Fran M. Krogstad</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Ohio</region></placeName><wicri:cityArea>College of Pharmacy, Division of Basic Pharmaceutical Sciences, Xavier University of Louisiana, 1 Drexel Drive,New Orleans, Louisiana 70125, Departments of Tropical Medicine and Medicine, Center for Infectious Diseases,Tulane University, 1430 Tulane Avenue, New Orleans, Louisiana 70112, and Department of Internal Medicine,Division of Infectious Diseases, College of Medicine, University of Cincinnati, Cincinnati</wicri:cityArea></affiliation><affiliation></affiliation></author><author><name sortKey="Krogstad, Donald J" sort="Krogstad, Donald J" uniqKey="Krogstad D" first="Donald J." last="Krogstad">Donald J. 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Chem.</title><idno type="ISSN">0022-2623</idno><idno type="eISSN">1520-4804</idno><imprint><publisher>American Chemical Society</publisher><date type="e-published" when="2004-04-14">2004</date><date when="2004-05-06">2004</date><biblScope unit="vol">47</biblScope><biblScope unit="issue">10</biblScope><biblScope unit="page" from="2700">2700</biblScope><biblScope unit="page" to="2705">2705</biblScope></imprint><idno type="ISSN">0022-2623</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0022-2623</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amidine</term><term>Animals</term><term>Antimalarial</term><term>Antimalarials (chemical synthesis)</term><term>Antimalarials (chemistry)</term><term>Antimalarials (pharmacology)</term><term>Antiprotozoal agent</term><term>Cell Line, Tumor</term><term>Cell line</term><term>Cell-Free System</term><term>Chemical synthesis</term><term>Chloroquine (pharmacology)</term><term>Combinatorial chemistry</term><term>Cytotoxicity</term><term>Drug Resistance</term><term>Hemin (metabolism)</term><term>Human</term><term>Humans</term><term>In vitro</term><term>Liquid phase</term><term>Lung</term><term>Molecular Conformation</term><term>Molecular rigidity</term><term>Nitrogen heterocycle</term><term>Parasiticide</term><term>Pentamidine</term><term>Piperazine derivatives</term><term>Plasmodium falciparum</term><term>Plasmodium falciparum (drug effects)</term><term>Steric hindrance</term><term>Structure activity relation</term><term>Structure-Activity Relationship</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Antipaludiques ()</term><term>Antipaludiques (pharmacologie)</term><term>Antipaludiques (synthèse chimique)</term><term>Chloroquine (pharmacologie)</term><term>Conformation moléculaire</term><term>Humains</term><term>Hémine (métabolisme)</term><term>Lignée cellulaire tumorale</term><term>Plasmodium falciparum ()</term><term>Relation structure-activité</term><term>Résistance aux substances</term><term>Système acellulaire</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemical synthesis" xml:lang="en"><term>Antimalarials</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Antimalarials</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Hemin</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antimalarials</term><term>Chloroquine</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Plasmodium falciparum</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Hémine</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Antipaludiques</term><term>Chloroquine</term></keywords><keywords scheme="MESH" qualifier="synthèse chimique" xml:lang="fr"><term>Antipaludiques</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cell Line, Tumor</term><term>Cell-Free System</term><term>Drug Resistance</term><term>Humans</term><term>Molecular Conformation</term><term>Structure-Activity Relationship</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Antipaludiques</term><term>Conformation moléculaire</term><term>Humains</term><term>Lignée cellulaire tumorale</term><term>Plasmodium falciparum</term><term>Relation structure-activité</term><term>Résistance aux substances</term><term>Système acellulaire</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Amidine</term><term>Antipaludique</term><term>Antiparasitaire</term><term>Antiprotozoaire</term><term>Benzamidine dérivé</term><term>Chimie combinatoire</term><term>Cytotoxicité</term><term>Encombrement stérique</term><term>Homme</term><term>Hétérocycle azote</term><term>In vitro</term><term>Lignée A549</term><term>Lignée cellulaire</term><term>Pentamidine</term><term>Phase liquide</term><term>Pipérazine dérivé</term><term>Pipérazine(1,4-bis[4-(1-alkylamidino)phényl])</term><term>Plasmodium falciparum</term><term>Poumon</term><term>Relation structure activité</term><term>Rigidité moléculaire</term><term>Synthèse chimique</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Homme</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract">Conformationally restricted bisbenzamidines and related congeners have been synthesized and evaluated for activity against two Plasmodium falciparum strains. The most active compounds, bisbenzamidines linked by a 1,4-piperazinediyl core, had IC50 values between 3 and 18 nM against both chloroquine-susceptible and -resistant parasites and IC50 values for cytotoxicity greater than 5 μM, using the A549 human lung epithelial cell line. DNA binding affinity, as estimated by ΔTm, did not correlate with either antiparasite effects or cytotoxicity. Each of the active bisbenzamidines interfered with the formation of hemozoin in cell-free systems.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Ohio</li></region></list><tree><country name="États-Unis"><region name="Ohio"><name sortKey="Mayence, Annie" sort="Mayence, Annie" uniqKey="Mayence A" first="Annie" last="Mayence">Annie Mayence</name></region><name sortKey="Cushion, Melanie T" sort="Cushion, Melanie T" uniqKey="Cushion M" first="Melanie T." last="Cushion">Melanie T. Cushion</name><name sortKey="Huang, Tien L" sort="Huang, Tien L" uniqKey="Huang T" first="Tien L." last="Huang">Tien L. Huang</name><name sortKey="Huang, Tien L" sort="Huang, Tien L" uniqKey="Huang T" first="Tien L." last="Huang">Tien L. Huang</name><name sortKey="Krogstad, Donald J" sort="Krogstad, Donald J" uniqKey="Krogstad D" first="Donald J." last="Krogstad">Donald J. Krogstad</name><name sortKey="Krogstad, Fran M" sort="Krogstad, Fran M" uniqKey="Krogstad F" first="Fran M." last="Krogstad">Fran M. Krogstad</name><name sortKey="Vanden Eynde, Jean Jacques" sort="Vanden Eynde, Jean Jacques" uniqKey="Vanden Eynde J" first="Jean Jacques" last="Vanden Eynde">Jean Jacques Vanden Eynde</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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