SrasV1, PascalFrancis, Curation, bibRecord, 000924

Biflavonoids of Dacrydium balansae with Potent Inhibitory Activity on Dengue 2 NS5 Polymerase

Identifieur interne : 000924 ( PascalFrancis/Curation ); précédent : 000923; suivant : 000925

Biflavonoids of Dacrydium balansae with Potent Inhibitory Activity on Dengue 2 NS5 Polymerase

Auteurs : Paul Coulerie [France] ; Cécilia Eydoux [France] ; Edouard Hnawia [France] ; Laetttia Stuhl [France] ; Alexandre Maciuk [France] ; Nicolas Lebouvier [France] ; Bruno Canard [France] ; Bruno Figadere [France] ; Jean-Claude Guillemot [France] ; Mohammed Nour [France]

Source :

Planta medica [ 0032-0943 ] ; 2012.

RBID : Pascal:12-0212137

Descripteurs français

Pascal (Inist)
- Flavonoïde, Dengue 2, Coniferales, Virus dengue, Pharmacognosie, Plante médicinale, Origine végétale, Podocarpaceae.
Wicri :
- topic : Plante médicinale.

English descriptors

KwdEn :
- Coniferales, Dengue 2, Dengue virus, Flavonoid, Medicinal plant, Pharmacognosy, Plant origin.

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 IC₅₀s between 0.26 and 3.12 uM. 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.

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C01	`01`		`ENG`	@0 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 IC₅₀s between 0.26 and 3.12 uM. 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.
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Pascal:12-0212137

Le document en format XML

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<author><name sortKey="Hnawia, Edouard" sort="Hnawia, Edouard" uniqKey="Hnawia E" first="Edouard" last="Hnawia">Edouard Hnawia</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Laboratoire Insulaire du Vivant et de l'Environnement, Université de la Nouvelle-Caledonie, Nouméa Cedex- Nouvelle-Calédonie</s1>
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<author><name sortKey="Stuhl, Laetttia" sort="Stuhl, Laetttia" uniqKey="Stuhl L" first="Laetttia" last="Stuhl">Laetttia Stuhl</name>
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<author><name sortKey="Maciuk, Alexandre" sort="Maciuk, Alexandre" uniqKey="Maciuk A" first="Alexandre" last="Maciuk">Alexandre Maciuk</name>
<affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Laboratoire de Pharmacognosie-Chimie des substances naturelles et chimiothérapies antiparasitaires, UMR CNRS 8076 BioCIS, Université Paris-Sud XI, Clément</s1>
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<author><name sortKey="Lebouvier, Nicolas" sort="Lebouvier, Nicolas" uniqKey="Lebouvier N" first="Nicolas" last="Lebouvier">Nicolas Lebouvier</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Laboratoire Insulaire du Vivant et de l'Environnement, Université de la Nouvelle-Caledonie, Nouméa Cedex- Nouvelle-Calédonie</s1>
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<author><name sortKey="Canard, Bruno" sort="Canard, Bruno" uniqKey="Canard B" first="Bruno" last="Canard">Bruno Canard</name>
<affiliation wicri:level="1"><inist:fA14 i1="02"><s1>AFMB, UMR 6098, Aix-Marseille Université, Campus de Luminy</s1>
<s2>Marseille</s2>
<s3>FRA</s3>
<sZ>2 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>9 aut.</sZ>
</inist:fA14>
<country>France</country>
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<author><name sortKey="Figadere, Bruno" sort="Figadere, Bruno" uniqKey="Figadere B" first="Bruno" last="Figadere">Bruno Figadere</name>
<affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Laboratoire de Pharmacognosie-Chimie des substances naturelles et chimiothérapies antiparasitaires, UMR CNRS 8076 BioCIS, Université Paris-Sud XI, Clément</s1>
<s2>Châtenay-Malabry</s2>
<s3>FRA</s3>
<sZ>5 aut.</sZ>
<sZ>8 aut.</sZ>
</inist:fA14>
<country>France</country>
</affiliation>
</author>
<author><name sortKey="Guillemot, Jean Claude" sort="Guillemot, Jean Claude" uniqKey="Guillemot J" first="Jean-Claude" last="Guillemot">Jean-Claude Guillemot</name>
<affiliation wicri:level="1"><inist:fA14 i1="02"><s1>AFMB, UMR 6098, Aix-Marseille Université, Campus de Luminy</s1>
<s2>Marseille</s2>
<s3>FRA</s3>
<sZ>2 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>9 aut.</sZ>
</inist:fA14>
<country>France</country>
</affiliation>
</author>
<author><name sortKey="Nour, Mohammed" sort="Nour, Mohammed" uniqKey="Nour M" first="Mohammed" last="Nour">Mohammed Nour</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Laboratoire Insulaire du Vivant et de l'Environnement, Université de la Nouvelle-Caledonie, Nouméa Cedex- Nouvelle-Calédonie</s1>
<s3>FRA</s3>
<sZ>1 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>10 aut.</sZ>
</inist:fA14>
<country>France</country>
</affiliation>
</author>
</analytic>
<series><title level="j" type="main">Planta medica</title>
<title level="j" type="abbreviated">Planta med.</title>
<idno type="ISSN">0032-0943</idno>
<imprint><date when="2012">2012</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt><title level="j" type="main">Planta medica</title>
<title level="j" type="abbreviated">Planta med.</title>
<idno type="ISSN">0032-0943</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Coniferales</term>
<term>Dengue 2</term>
<term>Dengue virus</term>
<term>Flavonoid</term>
<term>Medicinal plant</term>
<term>Pharmacognosy</term>
<term>Plant origin</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Flavonoïde</term>
<term>Dengue 2</term>
<term>Coniferales</term>
<term>Virus dengue</term>
<term>Pharmacognosie</term>
<term>Plante médicinale</term>
<term>Origine végétale</term>
<term>Podocarpaceae</term>
</keywords>
<keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Plante médicinale</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<sub>50</sub>
s between 0.26 and 3.12 uM. 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>
<inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0032-0943</s0>
</fA01>
<fA02 i1="01"><s0>PLMEAA</s0>
</fA02>
<fA03 i2="1"><s0>Planta med.</s0>
</fA03>
<fA05><s2>78</s2>
</fA05>
<fA06><s2>7</s2>
</fA06>
<fA08 i1="01" i2="1" l="ENG"><s1>Biflavonoids of Dacrydium balansae with Potent Inhibitory Activity on Dengue 2 NS5 Polymerase</s1>
</fA08>
<fA11 i1="01" i2="1"><s1>COULERIE (Paul)</s1>
</fA11>
<fA11 i1="02" i2="1"><s1>EYDOUX (Cécilia)</s1>
</fA11>
<fA11 i1="03" i2="1"><s1>HNAWIA (Edouard)</s1>
</fA11>
<fA11 i1="04" i2="1"><s1>STUHL (Laetttia)</s1>
</fA11>
<fA11 i1="05" i2="1"><s1>MACIUK (Alexandre)</s1>
</fA11>
<fA11 i1="06" i2="1"><s1>LEBOUVIER (Nicolas)</s1>
</fA11>
<fA11 i1="07" i2="1"><s1>CANARD (Bruno)</s1>
</fA11>
<fA11 i1="08" i2="1"><s1>FIGADERE (Bruno)</s1>
</fA11>
<fA11 i1="09" i2="1"><s1>GUILLEMOT (Jean-Claude)</s1>
</fA11>
<fA11 i1="10" i2="1"><s1>NOUR (Mohammed)</s1>
</fA11>
<fA14 i1="01"><s1>Laboratoire Insulaire du Vivant et de l'Environnement, Université de la Nouvelle-Caledonie, Nouméa Cedex- Nouvelle-Calédonie</s1>
<s3>FRA</s3>
<sZ>1 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>10 aut.</sZ>
</fA14>
<fA14 i1="02"><s1>AFMB, UMR 6098, Aix-Marseille Université, Campus de Luminy</s1>
<s2>Marseille</s2>
<s3>FRA</s3>
<sZ>2 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>9 aut.</sZ>
</fA14>
<fA14 i1="03"><s1>Laboratoire de Pharmacognosie-Chimie des substances naturelles et chimiothérapies antiparasitaires, UMR CNRS 8076 BioCIS, Université Paris-Sud XI, Clément</s1>
<s2>Châtenay-Malabry</s2>
<s3>FRA</s3>
<sZ>5 aut.</sZ>
<sZ>8 aut.</sZ>
</fA14>
<fA20><s1>672-677</s1>
</fA20>
<fA21><s1>2012</s1>
</fA21>
<fA23 i1="01"><s0>ENG</s0>
</fA23>
<fA43 i1="01"><s1>INIST</s1>
<s2>9624</s2>
<s5>354000506927230040</s5>
</fA43>
<fA44><s0>0000</s0>
<s1>© 2012 INIST-CNRS. All rights reserved.</s1>
</fA44>
<fA45><s0>21 ref.</s0>
</fA45>
<fA47 i1="01" i2="1"><s0>12-0212137</s0>
</fA47>
<fA60><s1>P</s1>
</fA60>
<fA61><s0>A</s0>
</fA61>
<fA64 i1="01" i2="1"><s0>Planta medica</s0>
</fA64>
<fA66 i1="01"><s0>DEU</s0>
</fA66>
<fC01 i1="01" l="ENG"><s0>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<sub>50</sub>
s between 0.26 and 3.12 uM. 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.</s0>
</fC01>
<fC02 i1="01" i2="X"><s0>002B02A04</s0>
</fC02>
<fC03 i1="01" i2="X" l="FRE"><s0>Flavonoïde</s0>
<s5>01</s5>
</fC03>
<fC03 i1="01" i2="X" l="ENG"><s0>Flavonoid</s0>
<s5>01</s5>
</fC03>
<fC03 i1="01" i2="X" l="SPA"><s0>Flavonoide</s0>
<s5>01</s5>
</fC03>
<fC03 i1="02" i2="X" l="FRE"><s0>Dengue 2</s0>
<s5>02</s5>
</fC03>
<fC03 i1="02" i2="X" l="ENG"><s0>Dengue 2</s0>
<s5>02</s5>
</fC03>
<fC03 i1="02" i2="X" l="SPA"><s0>Dengue 2</s0>
<s5>02</s5>
</fC03>
<fC03 i1="03" i2="X" l="FRE"><s0>Coniferales</s0>
<s2>NS</s2>
<s5>03</s5>
</fC03>
<fC03 i1="03" i2="X" l="ENG"><s0>Coniferales</s0>
<s2>NS</s2>
<s5>03</s5>
</fC03>
<fC03 i1="03" i2="X" l="SPA"><s0>Coniferales</s0>
<s2>NS</s2>
<s5>03</s5>
</fC03>
<fC03 i1="04" i2="X" l="FRE"><s0>Virus dengue</s0>
<s2>NW</s2>
<s5>04</s5>
</fC03>
<fC03 i1="04" i2="X" l="ENG"><s0>Dengue virus</s0>
<s2>NW</s2>
<s5>04</s5>
</fC03>
<fC03 i1="04" i2="X" l="SPA"><s0>Dengue virus</s0>
<s2>NW</s2>
<s5>04</s5>
</fC03>
<fC03 i1="05" i2="X" l="FRE"><s0>Pharmacognosie</s0>
<s5>05</s5>
</fC03>
<fC03 i1="05" i2="X" l="ENG"><s0>Pharmacognosy</s0>
<s5>05</s5>
</fC03>
<fC03 i1="05" i2="X" l="SPA"><s0>Farmacognosia</s0>
<s5>05</s5>
</fC03>
<fC03 i1="06" i2="X" l="FRE"><s0>Plante médicinale</s0>
<s5>06</s5>
</fC03>
<fC03 i1="06" i2="X" l="ENG"><s0>Medicinal plant</s0>
<s5>06</s5>
</fC03>
<fC03 i1="06" i2="X" l="SPA"><s0>Planta medicinal</s0>
<s5>06</s5>
</fC03>
<fC03 i1="07" i2="X" l="FRE"><s0>Origine végétale</s0>
<s5>23</s5>
</fC03>
<fC03 i1="07" i2="X" l="ENG"><s0>Plant origin</s0>
<s5>23</s5>
</fC03>
<fC03 i1="07" i2="X" l="SPA"><s0>Origen vegetal</s0>
<s5>23</s5>
</fC03>
<fC03 i1="08" i2="X" l="FRE"><s0>Podocarpaceae</s0>
<s4>INC</s4>
<s5>86</s5>
</fC03>
<fC07 i1="01" i2="X" l="FRE"><s0>Dengue</s0>
</fC07>
<fC07 i1="01" i2="X" l="ENG"><s0>Dengue</s0>
</fC07>
<fC07 i1="01" i2="X" l="SPA"><s0>Dengue</s0>
</fC07>
<fC07 i1="02" i2="X" l="FRE"><s0>Arbovirose</s0>
</fC07>
<fC07 i1="02" i2="X" l="ENG"><s0>Arbovirus disease</s0>
</fC07>
<fC07 i1="02" i2="X" l="SPA"><s0>Arbovirosis</s0>
</fC07>
<fC07 i1="03" i2="X" l="FRE"><s0>Virose</s0>
</fC07>
<fC07 i1="03" i2="X" l="ENG"><s0>Viral disease</s0>
</fC07>
<fC07 i1="03" i2="X" l="SPA"><s0>Virosis</s0>
</fC07>
<fC07 i1="04" i2="X" l="FRE"><s0>Infection</s0>
</fC07>
<fC07 i1="04" i2="X" l="ENG"><s0>Infection</s0>
</fC07>
<fC07 i1="04" i2="X" l="SPA"><s0>Infección</s0>
</fC07>
<fC07 i1="05" i2="X" l="FRE"><s0>Gymnospermae</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="05" i2="X" l="ENG"><s0>Gymnospermae</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="05" i2="X" l="SPA"><s0>Gymnospermae</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="06" i2="X" l="FRE"><s0>Spermatophyta</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="06" i2="X" l="ENG"><s0>Spermatophyta</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="06" i2="X" l="SPA"><s0>Spermatophyta</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="07" i2="X" l="FRE"><s0>Virus groupe dengue</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="07" i2="X" l="ENG"><s0>Dengue group virus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="07" i2="X" l="SPA"><s0>Dengue group virus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="08" i2="X" l="FRE"><s0>Flavivirus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="08" i2="X" l="ENG"><s0>Flavivirus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="08" i2="X" l="SPA"><s0>Flavivirus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="09" i2="X" l="FRE"><s0>Flaviviridae</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="09" i2="X" l="ENG"><s0>Flaviviridae</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="09" i2="X" l="SPA"><s0>Flaviviridae</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="10" i2="X" l="FRE"><s0>Virus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="10" i2="X" l="ENG"><s0>Virus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="10" i2="X" l="SPA"><s0>Virus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="11" i2="X" l="FRE"><s0>Polyphénol</s0>
<s5>37</s5>
</fC07>
<fC07 i1="11" i2="X" l="ENG"><s0>Polyphenol</s0>
<s5>37</s5>
</fC07>
<fC07 i1="11" i2="X" l="SPA"><s0>Polifenol</s0>
<s5>37</s5>
</fC07>
<fC07 i1="12" i2="X" l="FRE"><s0>Phénols</s0>
<s2>FX</s2>
<s5>38</s5>
</fC07>
<fC07 i1="12" i2="X" l="ENG"><s0>Phenols</s0>
<s2>FX</s2>
<s5>38</s5>
</fC07>
<fC07 i1="12" i2="X" l="SPA"><s0>Fenoles</s0>
<s2>FX</s2>
<s5>38</s5>
</fC07>
<fN21><s1>163</s1>
</fN21>
<fN44 i1="01"><s1>OTO</s1>
</fN44>
<fN82><s1>OTO</s1>
</fN82>
</pA>
</standard>
</inist>
</record>

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Biflavonoids of Dacrydium balansae with Potent Inhibitory Activity on Dengue 2 NS5 Polymerase

Biflavonoids of Dacrydium balansae with Potent Inhibitory Activity on Dengue 2 NS5 Polymerase

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