Synthesis, in vitro antimalarial activity and cytotoxicity of novel 4-aminoquinolinyl-chalcone amides.
Identifieur interne : 000235 ( Ncbi/Merge ); précédent : 000234; suivant : 000236Synthesis, in vitro antimalarial activity and cytotoxicity of novel 4-aminoquinolinyl-chalcone amides.
Auteurs : Frans J. Smit [Afrique du Sud] ; David D. N'Da [Afrique du Sud]Source :
- Bioorganic & medicinal chemistry [ 1464-3391 ] ; 2014.
Descripteurs français
- KwdFr :
- Amides (), Antipaludiques (), Antipaludiques (pharmacologie), Antipaludiques (synthèse chimique), Cellules cultivées, Chalcone (), Chloroquine (pharmacologie), Concentration inhibitrice 50, Diamines, Fibroblastes (), Humains, Lignée cellulaire (), Plasmodium falciparum (), Relation dose-effet des médicaments, Techniques de chimie synthétique.
- MESH :
- pharmacologie : Antipaludiques, Chloroquine.
- synthèse chimique : Antipaludiques.
- Amides, Antipaludiques, Cellules cultivées, Chalcone, Concentration inhibitrice 50, Diamines, Fibroblastes, Humains, Lignée cellulaire, Plasmodium falciparum, Relation dose-effet des médicaments, Techniques de chimie synthétique.
English descriptors
- KwdEn :
- Amides (chemistry), Antimalarials (chemical synthesis), Antimalarials (chemistry), Antimalarials (pharmacology), Cell Line (drug effects), Cells, Cultured, Chalcone (chemistry), Chemistry Techniques, Synthetic, Chloroquine (pharmacology), Diamines, Dose-Response Relationship, Drug, Fibroblasts (drug effects), Humans, Inhibitory Concentration 50, Plasmodium falciparum (drug effects).
- MESH :
- chemical , chemical synthesis : Antimalarials.
- chemical , chemistry : Amides, Antimalarials, Chalcone.
- chemical , pharmacology : Antimalarials, Chloroquine.
- drug effects : Cell Line, Fibroblasts, Plasmodium falciparum.
- Cells, Cultured, Chemistry Techniques, Synthetic, Diamines, Dose-Response Relationship, Drug, Humans, Inhibitory Concentration 50.
Abstract
A series of 4-aminoquinolinyl-chalcone amides 11-19 were synthesized through condensation of carboxylic acid-functionalized chalcone with aminoquinolines, using 1,1'-carbonyldiimidazole as coupling agent. These compounds were screened against the chloroquine sensitive (3D7) and chloroquine resistant (W2) strains of Plasmodium falciparum. Their cytotoxicity towards the WI-38 cell line of normal human fetal lung fibroblast was determined. All compounds were found active, with IC50 values ranging between 0.04-0.5μM and 0.07-1.8μM against 3D7 and W2, respectively. They demonstrated moderate to high selective activity towards the parasitic cells in the presence of mammalian cells. However, amide 15, featuring the 1,6-diaminohexane linker, despite possessing predicted unfavourable aqueous solubility and absorption properties, was the most active of all the amides tested. It was found to be as potent as CQ against 3D7, while it displayed a two-fold higher activity than CQ against the W2 strain, with good selective antimalarial activity (SI=435) towards the parasitic cells. During this study, amide 15 was thus identified as the best drug-candidate to for further investigation as a potential drug in search for new, safe and effective antimalarial drugs.
DOI: 10.1016/j.bmc.2013.12.032
PubMed: 24411478
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Electronic address: david.nda@nwu.ac.za.</nlm:affiliation><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea>Center of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom 2520</wicri:regionArea><wicri:noRegion>Potchefstroom 2520</wicri:noRegion></affiliation></author></analytic><series><title level="j">Bioorganic & medicinal chemistry</title><idno type="eISSN">1464-3391</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amides (chemistry)</term><term>Antimalarials (chemical synthesis)</term><term>Antimalarials (chemistry)</term><term>Antimalarials (pharmacology)</term><term>Cell Line (drug effects)</term><term>Cells, Cultured</term><term>Chalcone (chemistry)</term><term>Chemistry Techniques, Synthetic</term><term>Chloroquine (pharmacology)</term><term>Diamines</term><term>Dose-Response Relationship, Drug</term><term>Fibroblasts (drug effects)</term><term>Humans</term><term>Inhibitory Concentration 50</term><term>Plasmodium falciparum (drug effects)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Amides ()</term><term>Antipaludiques ()</term><term>Antipaludiques (pharmacologie)</term><term>Antipaludiques (synthèse chimique)</term><term>Cellules cultivées</term><term>Chalcone ()</term><term>Chloroquine (pharmacologie)</term><term>Concentration inhibitrice 50</term><term>Diamines</term><term>Fibroblastes ()</term><term>Humains</term><term>Lignée cellulaire ()</term><term>Plasmodium falciparum ()</term><term>Relation dose-effet des médicaments</term><term>Techniques de chimie synthétique</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>Amides</term><term>Antimalarials</term><term>Chalcone</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>Cell Line</term><term>Fibroblasts</term><term>Plasmodium falciparum</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>Cells, Cultured</term><term>Chemistry Techniques, Synthetic</term><term>Diamines</term><term>Dose-Response Relationship, Drug</term><term>Humans</term><term>Inhibitory Concentration 50</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Amides</term><term>Antipaludiques</term><term>Cellules cultivées</term><term>Chalcone</term><term>Concentration inhibitrice 50</term><term>Diamines</term><term>Fibroblastes</term><term>Humains</term><term>Lignée cellulaire</term><term>Plasmodium falciparum</term><term>Relation dose-effet des médicaments</term><term>Techniques de chimie synthétique</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">A series of 4-aminoquinolinyl-chalcone amides 11-19 were synthesized through condensation of carboxylic acid-functionalized chalcone with aminoquinolines, using 1,1'-carbonyldiimidazole as coupling agent. These compounds were screened against the chloroquine sensitive (3D7) and chloroquine resistant (W2) strains of Plasmodium falciparum. Their cytotoxicity towards the WI-38 cell line of normal human fetal lung fibroblast was determined. All compounds were found active, with IC50 values ranging between 0.04-0.5μM and 0.07-1.8μM against 3D7 and W2, respectively. They demonstrated moderate to high selective activity towards the parasitic cells in the presence of mammalian cells. However, amide 15, featuring the 1,6-diaminohexane linker, despite possessing predicted unfavourable aqueous solubility and absorption properties, was the most active of all the amides tested. It was found to be as potent as CQ against 3D7, while it displayed a two-fold higher activity than CQ against the W2 strain, with good selective antimalarial activity (SI=435) towards the parasitic cells. During this study, amide 15 was thus identified as the best drug-candidate to for further investigation as a potential drug in search for new, safe and effective antimalarial drugs. </div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">24411478</PMID><DateCompleted><Year>2014</Year><Month>10</Month><Day>28</Day></DateCompleted><DateRevised><Year>2014</Year><Month>01</Month><Day>24</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1464-3391</ISSN><JournalIssue CitedMedium="Internet"><Volume>22</Volume><Issue>3</Issue><PubDate><Year>2014</Year><Month>Feb</Month><Day>01</Day></PubDate></JournalIssue><Title>Bioorganic & medicinal chemistry</Title><ISOAbbreviation>Bioorg. Med. Chem.</ISOAbbreviation></Journal><ArticleTitle>Synthesis, in vitro antimalarial activity and cytotoxicity of novel 4-aminoquinolinyl-chalcone amides.</ArticleTitle><Pagination><MedlinePgn>1128-38</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.bmc.2013.12.032</ELocationID><ELocationID EIdType="pii" ValidYN="Y">S0968-0896(13)01040-7</ELocationID><Abstract><AbstractText>A series of 4-aminoquinolinyl-chalcone amides 11-19 were synthesized through condensation of carboxylic acid-functionalized chalcone with aminoquinolines, using 1,1'-carbonyldiimidazole as coupling agent. These compounds were screened against the chloroquine sensitive (3D7) and chloroquine resistant (W2) strains of Plasmodium falciparum. Their cytotoxicity towards the WI-38 cell line of normal human fetal lung fibroblast was determined. All compounds were found active, with IC50 values ranging between 0.04-0.5μM and 0.07-1.8μM against 3D7 and W2, respectively. They demonstrated moderate to high selective activity towards the parasitic cells in the presence of mammalian cells. However, amide 15, featuring the 1,6-diaminohexane linker, despite possessing predicted unfavourable aqueous solubility and absorption properties, was the most active of all the amides tested. It was found to be as potent as CQ against 3D7, while it displayed a two-fold higher activity than CQ against the W2 strain, with good selective antimalarial activity (SI=435) towards the parasitic cells. During this study, amide 15 was thus identified as the best drug-candidate to for further investigation as a potential drug in search for new, safe and effective antimalarial drugs. </AbstractText><CopyrightInformation>Copyright © 2013 Elsevier Ltd. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Smit</LastName><ForeName>Frans J</ForeName><Initials>FJ</Initials><AffiliationInfo><Affiliation>Pharmaceutical Chemistry, School of Pharmacy, North-West University, Potchefstroom 2520, South Africa.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>N'da</LastName><ForeName>David D</ForeName><Initials>DD</Initials><AffiliationInfo><Affiliation>Center of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom 2520, South Africa. Electronic address: david.nda@nwu.ac.za.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2013</Year><Month>12</Month><Day>22</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Bioorg Med Chem</MedlineTA><NlmUniqueID>9413298</NlmUniqueID><ISSNLinking>0968-0896</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000577">Amides</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000962">Antimalarials</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D003959">Diamines</NameOfSubstance></Chemical><Chemical><RegistryNumber>5S5A2Q39HX</RegistryNumber><NameOfSubstance UI="D002599">Chalcone</NameOfSubstance></Chemical><Chemical><RegistryNumber>886U3H6UFF</RegistryNumber><NameOfSubstance UI="D002738">Chloroquine</NameOfSubstance></Chemical><Chemical><RegistryNumber>ZRA5J5B2QW</RegistryNumber><NameOfSubstance UI="C007297">1,6-diaminohexane</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000577" MajorTopicYN="N">Amides</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000962" MajorTopicYN="N">Antimalarials</DescriptorName><QualifierName UI="Q000138" MajorTopicYN="N">chemical synthesis</QualifierName><QualifierName UI="Q000737" MajorTopicYN="Y">chemistry</QualifierName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002460" MajorTopicYN="N">Cell Line</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002478" MajorTopicYN="N">Cells, Cultured</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002599" MajorTopicYN="N">Chalcone</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="Y">chemistry</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D060326" MajorTopicYN="N">Chemistry Techniques, Synthetic</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002738" MajorTopicYN="N">Chloroquine</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D003959" MajorTopicYN="N">Diamines</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004305" MajorTopicYN="N">Dose-Response Relationship, Drug</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005347" MajorTopicYN="N">Fibroblasts</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D020128" MajorTopicYN="N">Inhibitory Concentration 50</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010963" MajorTopicYN="N">Plasmodium falciparum</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">4-Aminoquinoline</Keyword><Keyword MajorTopicYN="N">Chalcone</Keyword><Keyword MajorTopicYN="N">Chloroquine (CQ)</Keyword><Keyword MajorTopicYN="N">Malaria</Keyword><Keyword MajorTopicYN="N">Plasmodium falciparum</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2013</Year><Month>10</Month><Day>08</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2013</Year><Month>12</Month><Day>02</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2013</Year><Month>12</Month><Day>12</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2014</Year><Month>1</Month><Day>14</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2014</Year><Month>1</Month><Day>15</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2014</Year><Month>10</Month><Day>29</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">24411478</ArticleId><ArticleId IdType="pii">S0968-0896(13)01040-7</ArticleId><ArticleId IdType="doi">10.1016/j.bmc.2013.12.032</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Afrique du Sud</li></country></list><tree><country name="Afrique du Sud"><noRegion><name sortKey="Smit, Frans J" sort="Smit, Frans J" uniqKey="Smit F" first="Frans J" last="Smit">Frans J. Smit</name></noRegion><name sortKey="N Da, David D" sort="N Da, David D" uniqKey="N Da D" first="David D" last="N'Da">David D. N'Da</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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