Synthesis and SARs of indole-based α-amino acids as potent HIV-1 non-nucleoside reverse transcriptase inhibitors.
Identifieur interne : 001560 ( Main/Exploration ); précédent : 001559; suivant : 001561Synthesis and SARs of indole-based α-amino acids as potent HIV-1 non-nucleoside reverse transcriptase inhibitors.
Auteurs : Xin Han [République populaire de Chine] ; Haoming Wu ; Wei Wang ; Chune Dong ; Po Tien ; Shuwen Wu ; Hai-Bing ZhouSource :
- Organic & biomolecular chemistry [ 1477-0539 ] ; 2014.
Descripteurs français
- KwdFr :
- Acides aminés (), Acides aminés (pharmacologie), Acides aminés (synthèse chimique), Indoles (), Inhibiteurs de la transcriptase inverse (), Inhibiteurs de la transcriptase inverse (pharmacologie), Inhibiteurs de la transcriptase inverse (synthèse chimique), Modèles moléculaires, Relation dose-effet des médicaments, Relation structure-activité, Structure moléculaire, Transcriptase inverse du VIH (antagonistes et inhibiteurs), Transcriptase inverse du VIH (métabolisme).
- MESH :
- antagonistes et inhibiteurs : Transcriptase inverse du VIH.
- métabolisme : Transcriptase inverse du VIH.
- pharmacologie : Acides aminés, Inhibiteurs de la transcriptase inverse.
- synthèse chimique : Acides aminés, Inhibiteurs de la transcriptase inverse.
- Acides aminés, Indoles, Inhibiteurs de la transcriptase inverse, Modèles moléculaires, Relation dose-effet des médicaments, Relation structure-activité, Structure moléculaire.
English descriptors
- KwdEn :
- Amino Acids (chemical synthesis), Amino Acids (chemistry), Amino Acids (pharmacology), Dose-Response Relationship, Drug, HIV Reverse Transcriptase (antagonists & inhibitors), HIV Reverse Transcriptase (metabolism), Indoles (chemistry), Models, Molecular, Molecular Structure, Reverse Transcriptase Inhibitors (chemical synthesis), Reverse Transcriptase Inhibitors (chemistry), Reverse Transcriptase Inhibitors (pharmacology), Structure-Activity Relationship.
- MESH :
- chemical , antagonists & inhibitors : HIV Reverse Transcriptase.
- chemical , chemical synthesis : Amino Acids, Reverse Transcriptase Inhibitors.
- chemical , chemistry : Amino Acids, Indoles, Reverse Transcriptase Inhibitors.
- chemical , metabolism : HIV Reverse Transcriptase.
- chemical , pharmacology : Amino Acids, Reverse Transcriptase Inhibitors.
- Dose-Response Relationship, Drug, Models, Molecular, Molecular Structure, Structure-Activity Relationship.
Abstract
A series of non-nucleoside reverse transcriptase inhibitors derived from indole-based α-amino acids were designed and synthesized. Their inhibitory activities were detected by a TZM-bl cell assay on HIV virus type HIV-1IIIB. The comprehensive understanding of the SAR was obtained by utilizing the variation of the substituents of the indole-based α-amino acids. From the screened compounds, the novel inhibitors 19 and 29 were identified to be highly potent candidates with EC50 values of 0.060 μM and 0.045 μM respectively (CC50 values of 109.545 μM and 49.295 μM and SI values of 1825.8 and 1095.4). In most cases, the variation of substituents at different positions had a significant effect on the potency of activities. The results also indicate that the indole-based α-amino acids as efficient NNRTIs displayed comparable anti-HIV-1 activities to the reference drug NVP. We hope the identification of these indole-based amino acids as efficient NNRTIs of RT could stimulate researchers to develop more diversified anti-HIV drugs.
DOI: 10.1039/c4ob01333f
PubMed: 25209054
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: 000F35
- to stream PubMed, to step Curation: 000F35
- to stream PubMed, to step Checkpoint: 000F17
- to stream Ncbi, to step Merge: 002953
- to stream Ncbi, to step Curation: 002953
- to stream Ncbi, to step Checkpoint: 002953
- to stream Main, to step Merge: 001562
- to stream Main, to step Curation: 001560
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Synthesis and SARs of indole-based α-amino acids as potent HIV-1 non-nucleoside reverse transcriptase inhibitors.</title><author><name sortKey="Han, Xin" sort="Han, Xin" uniqKey="Han X" first="Xin" last="Han">Xin Han</name><affiliation wicri:level="4"><nlm:affiliation>School of Pharmaceutical Sciences, State Key Laboratory of Virology, Wuhan University, Wuhan, China430071.</nlm:affiliation><orgName type="university">Université de Wuhan</orgName><country>République populaire de Chine</country><placeName><settlement type="city">Wuhan</settlement><region type="province">Hubei</region></placeName></affiliation></author><author><name sortKey="Wu, Haoming" sort="Wu, Haoming" uniqKey="Wu H" first="Haoming" last="Wu">Haoming Wu</name></author><author><name sortKey="Wang, Wei" sort="Wang, Wei" uniqKey="Wang W" first="Wei" last="Wang">Wei Wang</name></author><author><name sortKey="Dong, Chune" sort="Dong, Chune" uniqKey="Dong C" first="Chune" last="Dong">Chune Dong</name></author><author><name sortKey="Tien, Po" sort="Tien, Po" uniqKey="Tien P" first="Po" last="Tien">Po Tien</name></author><author><name sortKey="Wu, Shuwen" sort="Wu, Shuwen" uniqKey="Wu S" first="Shuwen" last="Wu">Shuwen Wu</name></author><author><name sortKey="Zhou, Hai Bing" sort="Zhou, Hai Bing" uniqKey="Zhou H" first="Hai-Bing" last="Zhou">Hai-Bing Zhou</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2014">2014</date><idno type="RBID">pubmed:25209054</idno><idno type="pmid">25209054</idno><idno type="doi">10.1039/c4ob01333f</idno><idno type="wicri:Area/PubMed/Corpus">000F35</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000F35</idno><idno type="wicri:Area/PubMed/Curation">000F35</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000F35</idno><idno type="wicri:Area/PubMed/Checkpoint">000F17</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000F17</idno><idno type="wicri:Area/Ncbi/Merge">002953</idno><idno type="wicri:Area/Ncbi/Curation">002953</idno><idno type="wicri:Area/Ncbi/Checkpoint">002953</idno><idno type="wicri:Area/Main/Merge">001562</idno><idno type="wicri:Area/Main/Curation">001560</idno><idno type="wicri:Area/Main/Exploration">001560</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Synthesis and SARs of indole-based α-amino acids as potent HIV-1 non-nucleoside reverse transcriptase inhibitors.</title><author><name sortKey="Han, Xin" sort="Han, Xin" uniqKey="Han X" first="Xin" last="Han">Xin Han</name><affiliation wicri:level="4"><nlm:affiliation>School of Pharmaceutical Sciences, State Key Laboratory of Virology, Wuhan University, Wuhan, China430071.</nlm:affiliation><orgName type="university">Université de Wuhan</orgName><country>République populaire de Chine</country><placeName><settlement type="city">Wuhan</settlement><region type="province">Hubei</region></placeName></affiliation></author><author><name sortKey="Wu, Haoming" sort="Wu, Haoming" uniqKey="Wu H" first="Haoming" last="Wu">Haoming Wu</name></author><author><name sortKey="Wang, Wei" sort="Wang, Wei" uniqKey="Wang W" first="Wei" last="Wang">Wei Wang</name></author><author><name sortKey="Dong, Chune" sort="Dong, Chune" uniqKey="Dong C" first="Chune" last="Dong">Chune Dong</name></author><author><name sortKey="Tien, Po" sort="Tien, Po" uniqKey="Tien P" first="Po" last="Tien">Po Tien</name></author><author><name sortKey="Wu, Shuwen" sort="Wu, Shuwen" uniqKey="Wu S" first="Shuwen" last="Wu">Shuwen Wu</name></author><author><name sortKey="Zhou, Hai Bing" sort="Zhou, Hai Bing" uniqKey="Zhou H" first="Hai-Bing" last="Zhou">Hai-Bing Zhou</name></author></analytic><series><title level="j">Organic & biomolecular chemistry</title><idno type="eISSN">1477-0539</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acids (chemical synthesis)</term><term>Amino Acids (chemistry)</term><term>Amino Acids (pharmacology)</term><term>Dose-Response Relationship, Drug</term><term>HIV Reverse Transcriptase (antagonists & inhibitors)</term><term>HIV Reverse Transcriptase (metabolism)</term><term>Indoles (chemistry)</term><term>Models, Molecular</term><term>Molecular Structure</term><term>Reverse Transcriptase Inhibitors (chemical synthesis)</term><term>Reverse Transcriptase Inhibitors (chemistry)</term><term>Reverse Transcriptase Inhibitors (pharmacology)</term><term>Structure-Activity Relationship</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Acides aminés ()</term><term>Acides aminés (pharmacologie)</term><term>Acides aminés (synthèse chimique)</term><term>Indoles ()</term><term>Inhibiteurs de la transcriptase inverse ()</term><term>Inhibiteurs de la transcriptase inverse (pharmacologie)</term><term>Inhibiteurs de la transcriptase inverse (synthèse chimique)</term><term>Modèles moléculaires</term><term>Relation dose-effet des médicaments</term><term>Relation structure-activité</term><term>Structure moléculaire</term><term>Transcriptase inverse du VIH (antagonistes et inhibiteurs)</term><term>Transcriptase inverse du VIH (métabolisme)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>HIV Reverse Transcriptase</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemical synthesis" xml:lang="en"><term>Amino Acids</term><term>Reverse Transcriptase Inhibitors</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Amino Acids</term><term>Indoles</term><term>Reverse Transcriptase Inhibitors</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>HIV Reverse Transcriptase</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Amino Acids</term><term>Reverse Transcriptase Inhibitors</term></keywords><keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Transcriptase inverse du VIH</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Transcriptase inverse du VIH</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Acides aminés</term><term>Inhibiteurs de la transcriptase inverse</term></keywords><keywords scheme="MESH" qualifier="synthèse chimique" xml:lang="fr"><term>Acides aminés</term><term>Inhibiteurs de la transcriptase inverse</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Dose-Response Relationship, Drug</term><term>Models, Molecular</term><term>Molecular Structure</term><term>Structure-Activity Relationship</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Acides aminés</term><term>Indoles</term><term>Inhibiteurs de la transcriptase inverse</term><term>Modèles moléculaires</term><term>Relation dose-effet des médicaments</term><term>Relation structure-activité</term><term>Structure moléculaire</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">A series of non-nucleoside reverse transcriptase inhibitors derived from indole-based α-amino acids were designed and synthesized. Their inhibitory activities were detected by a TZM-bl cell assay on HIV virus type HIV-1IIIB. The comprehensive understanding of the SAR was obtained by utilizing the variation of the substituents of the indole-based α-amino acids. From the screened compounds, the novel inhibitors 19 and 29 were identified to be highly potent candidates with EC50 values of 0.060 μM and 0.045 μM respectively (CC50 values of 109.545 μM and 49.295 μM and SI values of 1825.8 and 1095.4). In most cases, the variation of substituents at different positions had a significant effect on the potency of activities. The results also indicate that the indole-based α-amino acids as efficient NNRTIs displayed comparable anti-HIV-1 activities to the reference drug NVP. We hope the identification of these indole-based amino acids as efficient NNRTIs of RT could stimulate researchers to develop more diversified anti-HIV drugs. </div></front></TEI><affiliations><list><country><li>République populaire de Chine</li></country><region><li>Hubei</li></region><settlement><li>Wuhan</li></settlement><orgName><li>Université de Wuhan</li></orgName></list><tree><noCountry><name sortKey="Dong, Chune" sort="Dong, Chune" uniqKey="Dong C" first="Chune" last="Dong">Chune Dong</name><name sortKey="Tien, Po" sort="Tien, Po" uniqKey="Tien P" first="Po" last="Tien">Po Tien</name><name sortKey="Wang, Wei" sort="Wang, Wei" uniqKey="Wang W" first="Wei" last="Wang">Wei Wang</name><name sortKey="Wu, Haoming" sort="Wu, Haoming" uniqKey="Wu H" first="Haoming" last="Wu">Haoming Wu</name><name sortKey="Wu, Shuwen" sort="Wu, Shuwen" uniqKey="Wu S" first="Shuwen" last="Wu">Shuwen Wu</name><name sortKey="Zhou, Hai Bing" sort="Zhou, Hai Bing" uniqKey="Zhou H" first="Hai-Bing" last="Zhou">Hai-Bing Zhou</name></noCountry><country name="République populaire de Chine"><region name="Hubei"><name sortKey="Han, Xin" sort="Han, Xin" uniqKey="Han X" first="Xin" last="Han">Xin Han</name></region></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 001560 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 001560 | 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:25209054
|texte= Synthesis and SARs of indole-based α-amino acids as potent HIV-1 non-nucleoside reverse transcriptase inhibitors.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:25209054" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a SrasV1
| This area was generated with Dilib version V0.6.33. |  |