Chemical library and structure-activity relationships of 11-demethyl-12-oxo calanolide A analogues as anti-HIV-1 agents.
Identifieur interne : 003148 ( Main/Exploration ); précédent : 003147; suivant : 003149Chemical library and structure-activity relationships of 11-demethyl-12-oxo calanolide A analogues as anti-HIV-1 agents.
Auteurs : Tao Ma [République populaire de Chine] ; Li Liu ; Hai Xue ; Li Li ; Chunyan Han ; Lin Wang ; Zhiwei Chen ; Gang LiuSource :
- Journal of medicinal chemistry [ 0022-2623 ] ; 2008.
Descripteurs français
- KwdFr :
- 4H-1-Benzopyran-4-ones (), 4H-1-Benzopyran-4-ones (pharmacologie), 4H-1-Benzopyran-4-ones (synthèse chimique), Agents antiVIH (), Agents antiVIH (pharmacologie), Agents antiVIH (synthèse chimique), Coumarines (), Coumarines (pharmacologie), Coumarines (synthèse chimique), Humains, Lignée cellulaire, Pyranocoumarines (), Pyranocoumarines (pharmacologie), Pyranocoumarines (synthèse chimique), Relation structure-activité, Stéréoisomérie, Techniques de chimie combinatoire, VIH-1 (Virus de l'Immunodéficience Humaine de type 1) ().
- MESH :
- pharmacologie : 4H-1-Benzopyran-4-ones, Agents antiVIH, Coumarines, Pyranocoumarines.
- synthèse chimique : 4H-1-Benzopyran-4-ones, Agents antiVIH, Coumarines, Pyranocoumarines.
- 4H-1-Benzopyran-4-ones, Agents antiVIH, Coumarines, Humains, Lignée cellulaire, Pyranocoumarines, Relation structure-activité, Stéréoisomérie, Techniques de chimie combinatoire, VIH-1 (Virus de l'Immunodéficience Humaine de type 1).
English descriptors
- KwdEn :
- Anti-HIV Agents (chemical synthesis), Anti-HIV Agents (chemistry), Anti-HIV Agents (pharmacology), Cell Line, Chromones (chemical synthesis), Chromones (chemistry), Chromones (pharmacology), Combinatorial Chemistry Techniques, Coumarins (chemical synthesis), Coumarins (chemistry), Coumarins (pharmacology), HIV-1 (drug effects), Humans, Pyranocoumarins (chemical synthesis), Pyranocoumarins (chemistry), Pyranocoumarins (pharmacology), Stereoisomerism, Structure-Activity Relationship.
- MESH :
- chemical , chemical synthesis : Anti-HIV Agents, Chromones, Coumarins, Pyranocoumarins.
- chemical , chemistry : Anti-HIV Agents, Chromones, Coumarins, Pyranocoumarins.
- chemical , pharmacology : Anti-HIV Agents, Chromones, Coumarins, Pyranocoumarins.
- drug effects : HIV-1.
- Cell Line, Combinatorial Chemistry Techniques, Humans, Stereoisomerism, Structure-Activity Relationship.
Abstract
(+)-Calanolide A ( 1) as a natural product was previously found as an inhibitor of HIV-1 reverse transcriptase. In our further investigation of its template, racemic 11-demethyl-12-oxo calanolide A ( 15), which had two fewer chiral carbon centers at the C-11 and C-12 positions than (+)-calanolide A, had a comparably inhibitory activity and better therapeutic index (EC 50 = 0.11 microM, TI = 818) against HIV-1 in vitro. A library based on its structural core was then designed and synthesized with introduction of nine diversity points in this article. The evaluations of anti-HIV-1 activity in vitro concluded their structure-activity relationships (SARs). A novel compound (10-bromomethyl-11-demethyl-12-oxo calanolide A, 123) was identified to have much higher inhibitory potency and therapeutic index (EC 50 = 2.85 nM, TI > 10,526) than those of the class compound against HIV-1. This finding provided a very important clue that modifications of the C ring at the C-10 position may be conducted to obtain drug candidates with better activity against HIV-1.
DOI: 10.1021/jm701405p
PubMed: 18284187
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: 001C10
- to stream PubMed, to step Curation: 001C10
- to stream PubMed, to step Checkpoint: 001B76
- to stream Ncbi, to step Merge: 001B81
- to stream Ncbi, to step Curation: 001B81
- to stream Ncbi, to step Checkpoint: 001B81
- to stream Main, to step Merge: 003243
- to stream Main, to step Curation: 003148
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Chemical library and structure-activity relationships of 11-demethyl-12-oxo calanolide A analogues as anti-HIV-1 agents.</title><author><name sortKey="Ma, Tao" sort="Ma, Tao" uniqKey="Ma T" first="Tao" last="Ma">Tao Ma</name><affiliation wicri:level="1"><nlm:affiliation>Department of Synthetic Medicinal Chemistry, Chinese Academy of Medical Sciences, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Synthetic Medicinal Chemistry, Chinese Academy of Medical Sciences</wicri:regionArea><wicri:noRegion>Chinese Academy of Medical Sciences</wicri:noRegion></affiliation></author><author><name sortKey="Liu, Li" sort="Liu, Li" uniqKey="Liu L" first="Li" last="Liu">Li Liu</name></author><author><name sortKey="Xue, Hai" sort="Xue, Hai" uniqKey="Xue H" first="Hai" last="Xue">Hai Xue</name></author><author><name sortKey="Li, Li" sort="Li, Li" uniqKey="Li L" first="Li" last="Li">Li Li</name></author><author><name sortKey="Han, Chunyan" sort="Han, Chunyan" uniqKey="Han C" first="Chunyan" last="Han">Chunyan Han</name></author><author><name sortKey="Wang, Lin" sort="Wang, Lin" uniqKey="Wang L" first="Lin" last="Wang">Lin Wang</name></author><author><name sortKey="Chen, Zhiwei" sort="Chen, Zhiwei" uniqKey="Chen Z" first="Zhiwei" last="Chen">Zhiwei Chen</name></author><author><name sortKey="Liu, Gang" sort="Liu, Gang" uniqKey="Liu G" first="Gang" last="Liu">Gang Liu</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2008">2008</date><idno type="RBID">pubmed:18284187</idno><idno type="pmid">18284187</idno><idno type="doi">10.1021/jm701405p</idno><idno type="wicri:Area/PubMed/Corpus">001C10</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001C10</idno><idno type="wicri:Area/PubMed/Curation">001C10</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001C10</idno><idno type="wicri:Area/PubMed/Checkpoint">001B76</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001B76</idno><idno type="wicri:Area/Ncbi/Merge">001B81</idno><idno type="wicri:Area/Ncbi/Curation">001B81</idno><idno type="wicri:Area/Ncbi/Checkpoint">001B81</idno><idno type="wicri:doubleKey">0022-2623:2008:Ma T:chemical:library:and</idno><idno type="wicri:Area/Main/Merge">003243</idno><idno type="wicri:Area/Main/Curation">003148</idno><idno type="wicri:Area/Main/Exploration">003148</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Chemical library and structure-activity relationships of 11-demethyl-12-oxo calanolide A analogues as anti-HIV-1 agents.</title><author><name sortKey="Ma, Tao" sort="Ma, Tao" uniqKey="Ma T" first="Tao" last="Ma">Tao Ma</name><affiliation wicri:level="1"><nlm:affiliation>Department of Synthetic Medicinal Chemistry, Chinese Academy of Medical Sciences, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Synthetic Medicinal Chemistry, Chinese Academy of Medical Sciences</wicri:regionArea><wicri:noRegion>Chinese Academy of Medical Sciences</wicri:noRegion></affiliation></author><author><name sortKey="Liu, Li" sort="Liu, Li" uniqKey="Liu L" first="Li" last="Liu">Li Liu</name></author><author><name sortKey="Xue, Hai" sort="Xue, Hai" uniqKey="Xue H" first="Hai" last="Xue">Hai Xue</name></author><author><name sortKey="Li, Li" sort="Li, Li" uniqKey="Li L" first="Li" last="Li">Li Li</name></author><author><name sortKey="Han, Chunyan" sort="Han, Chunyan" uniqKey="Han C" first="Chunyan" last="Han">Chunyan Han</name></author><author><name sortKey="Wang, Lin" sort="Wang, Lin" uniqKey="Wang L" first="Lin" last="Wang">Lin Wang</name></author><author><name sortKey="Chen, Zhiwei" sort="Chen, Zhiwei" uniqKey="Chen Z" first="Zhiwei" last="Chen">Zhiwei Chen</name></author><author><name sortKey="Liu, Gang" sort="Liu, Gang" uniqKey="Liu G" first="Gang" last="Liu">Gang Liu</name></author></analytic><series><title level="j">Journal of medicinal chemistry</title><idno type="ISSN">0022-2623</idno><imprint><date when="2008" type="published">2008</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Anti-HIV Agents (chemical synthesis)</term><term>Anti-HIV Agents (chemistry)</term><term>Anti-HIV Agents (pharmacology)</term><term>Cell Line</term><term>Chromones (chemical synthesis)</term><term>Chromones (chemistry)</term><term>Chromones (pharmacology)</term><term>Combinatorial Chemistry Techniques</term><term>Coumarins (chemical synthesis)</term><term>Coumarins (chemistry)</term><term>Coumarins (pharmacology)</term><term>HIV-1 (drug effects)</term><term>Humans</term><term>Pyranocoumarins (chemical synthesis)</term><term>Pyranocoumarins (chemistry)</term><term>Pyranocoumarins (pharmacology)</term><term>Stereoisomerism</term><term>Structure-Activity Relationship</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>4H-1-Benzopyran-4-ones ()</term><term>4H-1-Benzopyran-4-ones (pharmacologie)</term><term>4H-1-Benzopyran-4-ones (synthèse chimique)</term><term>Agents antiVIH ()</term><term>Agents antiVIH (pharmacologie)</term><term>Agents antiVIH (synthèse chimique)</term><term>Coumarines ()</term><term>Coumarines (pharmacologie)</term><term>Coumarines (synthèse chimique)</term><term>Humains</term><term>Lignée cellulaire</term><term>Pyranocoumarines ()</term><term>Pyranocoumarines (pharmacologie)</term><term>Pyranocoumarines (synthèse chimique)</term><term>Relation structure-activité</term><term>Stéréoisomérie</term><term>Techniques de chimie combinatoire</term><term>VIH-1 (Virus de l'Immunodéficience Humaine de type 1) ()</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemical synthesis" xml:lang="en"><term>Anti-HIV Agents</term><term>Chromones</term><term>Coumarins</term><term>Pyranocoumarins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Anti-HIV Agents</term><term>Chromones</term><term>Coumarins</term><term>Pyranocoumarins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Anti-HIV Agents</term><term>Chromones</term><term>Coumarins</term><term>Pyranocoumarins</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>HIV-1</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>4H-1-Benzopyran-4-ones</term><term>Agents antiVIH</term><term>Coumarines</term><term>Pyranocoumarines</term></keywords><keywords scheme="MESH" qualifier="synthèse chimique" xml:lang="fr"><term>4H-1-Benzopyran-4-ones</term><term>Agents antiVIH</term><term>Coumarines</term><term>Pyranocoumarines</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Cell Line</term><term>Combinatorial Chemistry Techniques</term><term>Humans</term><term>Stereoisomerism</term><term>Structure-Activity Relationship</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>4H-1-Benzopyran-4-ones</term><term>Agents antiVIH</term><term>Coumarines</term><term>Humains</term><term>Lignée cellulaire</term><term>Pyranocoumarines</term><term>Relation structure-activité</term><term>Stéréoisomérie</term><term>Techniques de chimie combinatoire</term><term>VIH-1 (Virus de l'Immunodéficience Humaine de type 1)</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">(+)-Calanolide A ( 1) as a natural product was previously found as an inhibitor of HIV-1 reverse transcriptase. In our further investigation of its template, racemic 11-demethyl-12-oxo calanolide A ( 15), which had two fewer chiral carbon centers at the C-11 and C-12 positions than (+)-calanolide A, had a comparably inhibitory activity and better therapeutic index (EC 50 = 0.11 microM, TI = 818) against HIV-1 in vitro. A library based on its structural core was then designed and synthesized with introduction of nine diversity points in this article. The evaluations of anti-HIV-1 activity in vitro concluded their structure-activity relationships (SARs). A novel compound (10-bromomethyl-11-demethyl-12-oxo calanolide A, 123) was identified to have much higher inhibitory potency and therapeutic index (EC 50 = 2.85 nM, TI > 10,526) than those of the class compound against HIV-1. This finding provided a very important clue that modifications of the C ring at the C-10 position may be conducted to obtain drug candidates with better activity against HIV-1.</div></front></TEI><affiliations><list><country><li>République populaire de Chine</li></country></list><tree><noCountry><name sortKey="Chen, Zhiwei" sort="Chen, Zhiwei" uniqKey="Chen Z" first="Zhiwei" last="Chen">Zhiwei Chen</name><name sortKey="Han, Chunyan" sort="Han, Chunyan" uniqKey="Han C" first="Chunyan" last="Han">Chunyan Han</name><name sortKey="Li, Li" sort="Li, Li" uniqKey="Li L" first="Li" last="Li">Li Li</name><name sortKey="Liu, Gang" sort="Liu, Gang" uniqKey="Liu G" first="Gang" last="Liu">Gang Liu</name><name sortKey="Liu, Li" sort="Liu, Li" uniqKey="Liu L" first="Li" last="Liu">Li Liu</name><name sortKey="Wang, Lin" sort="Wang, Lin" uniqKey="Wang L" first="Lin" last="Wang">Lin Wang</name><name sortKey="Xue, Hai" sort="Xue, Hai" uniqKey="Xue H" first="Hai" last="Xue">Hai Xue</name></noCountry><country name="République populaire de Chine"><noRegion><name sortKey="Ma, Tao" sort="Ma, Tao" uniqKey="Ma T" first="Tao" last="Ma">Tao Ma</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/SrasV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 003148 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 003148 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= SrasV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= pubmed:18284187
|texte= Chemical library and structure-activity relationships of 11-demethyl-12-oxo calanolide A analogues as anti-HIV-1 agents.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:18284187" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a SrasV1
| This area was generated with Dilib version V0.6.33. |  |