Biflavonoids of Dacrydium balansae with potent inhibitory activity on dengue 2 NS5 polymerase.
Identifieur interne : 000176 ( France/Analysis ); précédent : 000175; suivant : 000177Biflavonoids of Dacrydium balansae with potent inhibitory activity on dengue 2 NS5 polymerase.
Auteurs : Paul Coulerie [France] ; Cécilia Eydoux ; Edouard Hnawia ; Laetitia Stuhl ; Alexandre Maciuk ; Nicolas Lebouvier ; Bruno Canard ; Bruno Figadère ; Jean-Claude Guillemot ; Mohammed NourSource :
- Planta medica [ 1439-0221 ] ; 2012.
Descripteurs français
- KwdFr :
- Antienzymes (pharmacologie), Antiviraux (), Antiviraux (pharmacologie), Biflavonoïdes (), Biflavonoïdes (pharmacologie), DNA-directed RNA polymerases (), DNA-directed RNA polymerases (antagonistes et inhibiteurs), Feuilles de plante (), Nouvelle-Calédonie, Phytothérapie, Protéines virales non structurales (métabolisme), RNA replicase (antagonistes et inhibiteurs), Relation structure-activité, Virus de la dengue (), Virus de la dengue (enzymologie), Écorce ().
- MESH :
- antagonistes et inhibiteurs : DNA-directed RNA polymerases, RNA replicase.
- enzymologie : Virus de la dengue.
- métabolisme : Protéines virales non structurales.
- pharmacologie : Antienzymes, Antiviraux, Biflavonoïdes.
- Antiviraux, Biflavonoïdes, DNA-directed RNA polymerases, Feuilles de plante, Nouvelle-Calédonie, Phytothérapie, Relation structure-activité, Virus de la dengue, Écorce.
English descriptors
- KwdEn :
- Antiviral Agents (chemistry), Antiviral Agents (pharmacology), Biflavonoids (chemistry), Biflavonoids (pharmacology), DNA-Directed RNA Polymerases (antagonists & inhibitors), DNA-Directed RNA Polymerases (chemistry), Dengue Virus (drug effects), Dengue Virus (enzymology), Enzyme Inhibitors (pharmacology), New Caledonia, Phytotherapy, Plant Bark (chemistry), Plant Leaves (chemistry), RNA Replicase (antagonists & inhibitors), Structure-Activity Relationship, Tracheophyta (chemistry), Viral Nonstructural Proteins (metabolism).
- MESH :
- chemical , antagonists & inhibitors : DNA-Directed RNA Polymerases, RNA Replicase.
- chemical , chemistry : Antiviral Agents, Biflavonoids, DNA-Directed RNA Polymerases.
- chemical , metabolism : Viral Nonstructural Proteins.
- chemical , pharmacology : Antiviral Agents, Biflavonoids, Enzyme Inhibitors.
- geographic : New Caledonia.
- chemistry : Plant Bark, Plant Leaves, Tracheophyta.
- drug effects : Dengue Virus.
- enzymology : Dengue Virus.
- Phytotherapy, Structure-Activity Relationship.
Abstract
In order to find new molecules for antiviral drug design, we screened 102 ethyl acetate extracts from New-Caledonian flora for antiviral activity against the dengue 2 virus RNA-dependant RNA polymerase (DV-NS5 RdRp). The leaf extract of Dacrydium balansae, which strongly inhibited the DV-NS5, was submitted to bioguided fractionation. Four biflavonoids ( 1- 4), three sterols ( 5- 7), and two stilbene derivatives ( 8- 9) were identified and evaluated for their antiviral potential on the DV-NS5 RdRp. Biflavonoids appeared to be potent inhibitors of DV-NS5 RdRp with IC (50)s between 0.26 and 3.12 µM. Inhibitory activity evaluations against the RNA polymerase from other Flaviviridae viruses allowed us to conclude that these compounds are specific inhibitors of the DV RNA polymerase. The strongest inhibitions were observed with hinokiflavone ( 4), but podocarpusflavone A ( 2) is the strongest noncytotoxic inhibitor of the DV-NS5 and it also displayed polymerase inhibitory activity in a DV replicon. A preliminary structure-activity relationship study (SARs) revealed the necessity of the biflavonoid skeleton, the influence of number and position of methoxylations, and the importance of a free rotation of the linkage between the two apigenin monomers of the biflavonoids. To the best of our knowledge, podocarpusflavone A ( 2) is the strongest noncytotoxic non-nucleotide molecule exhibiting a specific inhibitory activity against the RNA polymerase domain of DV-NS5 and thus is promising for chemotherapy development against dengue fever.
DOI: 10.1055/s-0031-1298355
PubMed: 22411725
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: 001386
- to stream PubMed, to step Curation: 001386
- to stream PubMed, to step Checkpoint: 001382
- to stream Ncbi, to step Merge: 002474
- to stream Ncbi, to step Curation: 002474
- to stream Ncbi, to step Checkpoint: 002474
- to stream Main, to step Merge: 001D81
- to stream Main, to step Curation: 001D58
- to stream Main, to step Exploration: 001D58
- to stream France, to step Extraction: 000176
Links to Exploration step
pubmed:22411725Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Biflavonoids of Dacrydium balansae with potent inhibitory activity on dengue 2 NS5 polymerase.</title><author><name sortKey="Coulerie, Paul" sort="Coulerie, Paul" uniqKey="Coulerie P" first="Paul" last="Coulerie">Paul Coulerie</name><affiliation wicri:level="1"><nlm:affiliation>Laboratoire Insulaire du Vivant et de l'Environnement, Université de la Nouvelle-Caledonie, Nouméa Cedex, Nouvelle-Calédonie, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire Insulaire du Vivant et de l'Environnement, Université de la Nouvelle-Caledonie, Nouméa Cedex, Nouvelle-Calédonie</wicri:regionArea><wicri:noRegion>Nouvelle-Calédonie</wicri:noRegion><wicri:noRegion>Nouvelle-Calédonie</wicri:noRegion></affiliation></author><author><name sortKey="Eydoux, Cecilia" sort="Eydoux, Cecilia" uniqKey="Eydoux C" first="Cécilia" last="Eydoux">Cécilia Eydoux</name></author><author><name sortKey="Hnawia, Edouard" sort="Hnawia, Edouard" uniqKey="Hnawia E" first="Edouard" last="Hnawia">Edouard Hnawia</name></author><author><name sortKey="Stuhl, Laetitia" sort="Stuhl, Laetitia" uniqKey="Stuhl L" first="Laetitia" last="Stuhl">Laetitia Stuhl</name></author><author><name sortKey="Maciuk, Alexandre" sort="Maciuk, Alexandre" uniqKey="Maciuk A" first="Alexandre" last="Maciuk">Alexandre Maciuk</name></author><author><name sortKey="Lebouvier, Nicolas" sort="Lebouvier, Nicolas" uniqKey="Lebouvier N" first="Nicolas" last="Lebouvier">Nicolas Lebouvier</name></author><author><name sortKey="Canard, Bruno" sort="Canard, Bruno" uniqKey="Canard B" first="Bruno" last="Canard">Bruno Canard</name></author><author><name sortKey="Figadere, Bruno" sort="Figadere, Bruno" uniqKey="Figadere B" first="Bruno" last="Figadère">Bruno Figadère</name></author><author><name sortKey="Guillemot, Jean Claude" sort="Guillemot, Jean Claude" uniqKey="Guillemot J" first="Jean-Claude" last="Guillemot">Jean-Claude Guillemot</name></author><author><name sortKey="Nour, Mohammed" sort="Nour, Mohammed" uniqKey="Nour M" first="Mohammed" last="Nour">Mohammed Nour</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2012">2012</date><idno type="RBID">pubmed:22411725</idno><idno type="pmid">22411725</idno><idno type="doi">10.1055/s-0031-1298355</idno><idno type="wicri:Area/PubMed/Corpus">001386</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001386</idno><idno type="wicri:Area/PubMed/Curation">001386</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001386</idno><idno type="wicri:Area/PubMed/Checkpoint">001382</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001382</idno><idno type="wicri:Area/Ncbi/Merge">002474</idno><idno type="wicri:Area/Ncbi/Curation">002474</idno><idno type="wicri:Area/Ncbi/Checkpoint">002474</idno><idno type="wicri:Area/Main/Merge">001D81</idno><idno type="wicri:Area/Main/Curation">001D58</idno><idno type="wicri:Area/Main/Exploration">001D58</idno><idno type="wicri:Area/France/Extraction">000176</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Biflavonoids of Dacrydium balansae with potent inhibitory activity on dengue 2 NS5 polymerase.</title><author><name sortKey="Coulerie, Paul" sort="Coulerie, Paul" uniqKey="Coulerie P" first="Paul" last="Coulerie">Paul Coulerie</name><affiliation wicri:level="1"><nlm:affiliation>Laboratoire Insulaire du Vivant et de l'Environnement, Université de la Nouvelle-Caledonie, Nouméa Cedex, Nouvelle-Calédonie, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire Insulaire du Vivant et de l'Environnement, Université de la Nouvelle-Caledonie, Nouméa Cedex, Nouvelle-Calédonie</wicri:regionArea><wicri:noRegion>Nouvelle-Calédonie</wicri:noRegion><wicri:noRegion>Nouvelle-Calédonie</wicri:noRegion></affiliation></author><author><name sortKey="Eydoux, Cecilia" sort="Eydoux, Cecilia" uniqKey="Eydoux C" first="Cécilia" last="Eydoux">Cécilia Eydoux</name></author><author><name sortKey="Hnawia, Edouard" sort="Hnawia, Edouard" uniqKey="Hnawia E" first="Edouard" last="Hnawia">Edouard Hnawia</name></author><author><name sortKey="Stuhl, Laetitia" sort="Stuhl, Laetitia" uniqKey="Stuhl L" first="Laetitia" last="Stuhl">Laetitia Stuhl</name></author><author><name sortKey="Maciuk, Alexandre" sort="Maciuk, Alexandre" uniqKey="Maciuk A" first="Alexandre" last="Maciuk">Alexandre Maciuk</name></author><author><name sortKey="Lebouvier, Nicolas" sort="Lebouvier, Nicolas" uniqKey="Lebouvier N" first="Nicolas" last="Lebouvier">Nicolas Lebouvier</name></author><author><name sortKey="Canard, Bruno" sort="Canard, Bruno" uniqKey="Canard B" first="Bruno" last="Canard">Bruno Canard</name></author><author><name sortKey="Figadere, Bruno" sort="Figadere, Bruno" uniqKey="Figadere B" first="Bruno" last="Figadère">Bruno Figadère</name></author><author><name sortKey="Guillemot, Jean Claude" sort="Guillemot, Jean Claude" uniqKey="Guillemot J" first="Jean-Claude" last="Guillemot">Jean-Claude Guillemot</name></author><author><name sortKey="Nour, Mohammed" sort="Nour, Mohammed" uniqKey="Nour M" first="Mohammed" last="Nour">Mohammed Nour</name></author></analytic><series><title level="j">Planta medica</title><idno type="eISSN">1439-0221</idno><imprint><date when="2012" type="published">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antiviral Agents (chemistry)</term><term>Antiviral Agents (pharmacology)</term><term>Biflavonoids (chemistry)</term><term>Biflavonoids (pharmacology)</term><term>DNA-Directed RNA Polymerases (antagonists & inhibitors)</term><term>DNA-Directed RNA Polymerases (chemistry)</term><term>Dengue Virus (drug effects)</term><term>Dengue Virus (enzymology)</term><term>Enzyme Inhibitors (pharmacology)</term><term>New Caledonia</term><term>Phytotherapy</term><term>Plant Bark (chemistry)</term><term>Plant Leaves (chemistry)</term><term>RNA Replicase (antagonists & inhibitors)</term><term>Structure-Activity Relationship</term><term>Tracheophyta (chemistry)</term><term>Viral Nonstructural Proteins (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Antienzymes (pharmacologie)</term><term>Antiviraux ()</term><term>Antiviraux (pharmacologie)</term><term>Biflavonoïdes ()</term><term>Biflavonoïdes (pharmacologie)</term><term>DNA-directed RNA polymerases ()</term><term>DNA-directed RNA polymerases (antagonistes et inhibiteurs)</term><term>Feuilles de plante ()</term><term>Nouvelle-Calédonie</term><term>Phytothérapie</term><term>Protéines virales non structurales (métabolisme)</term><term>RNA replicase (antagonistes et inhibiteurs)</term><term>Relation structure-activité</term><term>Virus de la dengue ()</term><term>Virus de la dengue (enzymologie)</term><term>Écorce ()</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>DNA-Directed RNA Polymerases</term><term>RNA Replicase</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Antiviral Agents</term><term>Biflavonoids</term><term>DNA-Directed RNA Polymerases</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Viral Nonstructural Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antiviral Agents</term><term>Biflavonoids</term><term>Enzyme Inhibitors</term></keywords><keywords scheme="MESH" type="geographic" xml:lang="en"><term>New Caledonia</term></keywords><keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>DNA-directed RNA polymerases</term><term>RNA replicase</term></keywords><keywords scheme="MESH" qualifier="chemistry" xml:lang="en"><term>Plant Bark</term><term>Plant Leaves</term><term>Tracheophyta</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Dengue Virus</term></keywords><keywords scheme="MESH" qualifier="enzymologie" xml:lang="fr"><term>Virus de la dengue</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Dengue Virus</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Protéines virales non structurales</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Antienzymes</term><term>Antiviraux</term><term>Biflavonoïdes</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Phytotherapy</term><term>Structure-Activity Relationship</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Antiviraux</term><term>Biflavonoïdes</term><term>DNA-directed RNA polymerases</term><term>Feuilles de plante</term><term>Nouvelle-Calédonie</term><term>Phytothérapie</term><term>Relation structure-activité</term><term>Virus de la dengue</term><term>Écorce</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">In order to find new molecules for antiviral drug design, we screened 102 ethyl acetate extracts from New-Caledonian flora for antiviral activity against the dengue 2 virus RNA-dependant RNA polymerase (DV-NS5 RdRp). The leaf extract of Dacrydium balansae, which strongly inhibited the DV-NS5, was submitted to bioguided fractionation. Four biflavonoids ( 1- 4), three sterols ( 5- 7), and two stilbene derivatives ( 8- 9) were identified and evaluated for their antiviral potential on the DV-NS5 RdRp. Biflavonoids appeared to be potent inhibitors of DV-NS5 RdRp with IC (50)s between 0.26 and 3.12 µM. Inhibitory activity evaluations against the RNA polymerase from other Flaviviridae viruses allowed us to conclude that these compounds are specific inhibitors of the DV RNA polymerase. The strongest inhibitions were observed with hinokiflavone ( 4), but podocarpusflavone A ( 2) is the strongest noncytotoxic inhibitor of the DV-NS5 and it also displayed polymerase inhibitory activity in a DV replicon. A preliminary structure-activity relationship study (SARs) revealed the necessity of the biflavonoid skeleton, the influence of number and position of methoxylations, and the importance of a free rotation of the linkage between the two apigenin monomers of the biflavonoids. To the best of our knowledge, podocarpusflavone A ( 2) is the strongest noncytotoxic non-nucleotide molecule exhibiting a specific inhibitory activity against the RNA polymerase domain of DV-NS5 and thus is promising for chemotherapy development against dengue fever.</div></front></TEI><affiliations><list><country><li>France</li></country></list><tree><noCountry><name sortKey="Canard, Bruno" sort="Canard, Bruno" uniqKey="Canard B" first="Bruno" last="Canard">Bruno Canard</name><name sortKey="Eydoux, Cecilia" sort="Eydoux, Cecilia" uniqKey="Eydoux C" first="Cécilia" last="Eydoux">Cécilia Eydoux</name><name sortKey="Figadere, Bruno" sort="Figadere, Bruno" uniqKey="Figadere B" first="Bruno" last="Figadère">Bruno Figadère</name><name sortKey="Guillemot, Jean Claude" sort="Guillemot, Jean Claude" uniqKey="Guillemot J" first="Jean-Claude" last="Guillemot">Jean-Claude Guillemot</name><name sortKey="Hnawia, Edouard" sort="Hnawia, Edouard" uniqKey="Hnawia E" first="Edouard" last="Hnawia">Edouard Hnawia</name><name sortKey="Lebouvier, Nicolas" sort="Lebouvier, Nicolas" uniqKey="Lebouvier N" first="Nicolas" last="Lebouvier">Nicolas Lebouvier</name><name sortKey="Maciuk, Alexandre" sort="Maciuk, Alexandre" uniqKey="Maciuk A" first="Alexandre" last="Maciuk">Alexandre Maciuk</name><name sortKey="Nour, Mohammed" sort="Nour, Mohammed" uniqKey="Nour M" first="Mohammed" last="Nour">Mohammed Nour</name><name sortKey="Stuhl, Laetitia" sort="Stuhl, Laetitia" uniqKey="Stuhl L" first="Laetitia" last="Stuhl">Laetitia Stuhl</name></noCountry><country name="France"><noRegion><name sortKey="Coulerie, Paul" sort="Coulerie, Paul" uniqKey="Coulerie P" first="Paul" last="Coulerie">Paul Coulerie</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/SrasV1/Data/France/Analysis
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000176 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/France/Analysis/biblio.hfd -nk 000176 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= SrasV1
|flux= France
|étape= Analysis
|type= RBID
|clé= pubmed:22411725
|texte= Biflavonoids of Dacrydium balansae with potent inhibitory activity on dengue 2 NS5 polymerase.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/France/Analysis/RBID.i -Sk "pubmed:22411725" \
| HfdSelect -Kh $EXPLOR_AREA/Data/France/Analysis/biblio.hfd \
| NlmPubMed2Wicri -a SrasV1
| This area was generated with Dilib version V0.6.33. |  |