SrasV1, Main, Exploration, bibRecord, 001051

Design, synthesis and evaluation of novel HIV-1 NNRTIs with dual structural conformations targeting the entrance channel of the NNRTI binding pocket.

Identifieur interne : 001051 ( Main/Exploration ); précédent : 001050; suivant : 001052

Design, synthesis and evaluation of novel HIV-1 NNRTIs with dual structural conformations targeting the entrance channel of the NNRTI binding pocket.

Auteurs : Qing Meng [République populaire de Chine] ; Xuwang Chen [République populaire de Chine] ; Dongwei Kang [République populaire de Chine] ; Boshi Huang [République populaire de Chine] ; Wenxin Li [République populaire de Chine] ; Peng Zhan [République populaire de Chine] ; Dirk Daelemans [Belgique] ; Erik De Clercq [Belgique] ; Christophe Pannecouque [Belgique] ; Xinyong Liu [République populaire de Chine]

Source :

European journal of medicinal chemistry [ 1768-3254 ] ; 2016.

RBID : pubmed:26994843

Descripteurs français

English descriptors

KwdEn :
- Anti-HIV Agents (chemical synthesis), Anti-HIV Agents (chemistry), Anti-HIV Agents (pharmacology), Binding Sites (drug effects), Dose-Response Relationship, Drug, Drug Design, HIV Reverse Transcriptase (antagonists & inhibitors), HIV Reverse Transcriptase (chemistry), HIV Reverse Transcriptase (metabolism), HIV-1 (drug effects), HIV-1 (genetics), Humans, Microbial Sensitivity Tests, Molecular Structure, Reverse Transcriptase Inhibitors (chemical synthesis), Reverse Transcriptase Inhibitors (chemistry), Reverse Transcriptase Inhibitors (pharmacology), Structure-Activity Relationship, Virus Replication (drug effects).
MESH :
- chemical , antagonists & inhibitors : HIV Reverse Transcriptase.
- chemical , chemical synthesis : Anti-HIV Agents, Reverse Transcriptase Inhibitors.
- chemical , chemistry : Anti-HIV Agents, HIV Reverse Transcriptase, Reverse Transcriptase Inhibitors.
- chemical , metabolism : HIV Reverse Transcriptase.
- chemical , pharmacology : Anti-HIV Agents, Reverse Transcriptase Inhibitors.
- drug effects : Binding Sites, HIV-1, Virus Replication.
- genetics : HIV-1.
- Dose-Response Relationship, Drug, Drug Design, Humans, Microbial Sensitivity Tests, Molecular Structure, Structure-Activity Relationship.

Abstract

On the basis of structure-based bioisosteric replacement and molecular hybridization strategy, a series of novel dual structural-conformation inhibitors targeting the "entrance channel" of HIV-1 NNRTIs binding pocket (NNIBP) were designed and synthesized. All of the new compounds were evaluated for their anti-HIV activities in MT-4 cells using the MTT method. Five compounds exhibited moderate to excellent potencies inhibiting wild-type (wt) HIV-1 replication with EC50 values ranging from 31.36 μM to 0.11 μM. Among them, compound 15b was identified as the most potent inhibitor with EC50 values of 0.11 μM and 2.18 μM against wt and K103N/Y181C double mutant HIV-1 strain (RES056), respectively. In addition, preliminary structure-activity relationships (SARs) and molecular simulation studies were discussed, which may provide valuable insights for further optimization.

DOI: 10.1016/j.ejmech.2016.02.068
PubMed: 26994843

Affiliations:

Belgique, République populaire de Chine

Le document en format XML

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<front><div type="abstract" xml:lang="en">On the basis of structure-based bioisosteric replacement and molecular hybridization strategy, a series of novel dual structural-conformation inhibitors targeting the "entrance channel" of HIV-1 NNRTIs binding pocket (NNIBP) were designed and synthesized. All of the new compounds were evaluated for their anti-HIV activities in MT-4 cells using the MTT method. Five compounds exhibited moderate to excellent potencies inhibiting wild-type (wt) HIV-1 replication with EC50 values ranging from 31.36 μM to 0.11 μM. Among them, compound 15b was identified as the most potent inhibitor with EC50 values of 0.11 μM and 2.18 μM against wt and K103N/Y181C double mutant HIV-1 strain (RES056), respectively. In addition, preliminary structure-activity relationships (SARs) and molecular simulation studies were discussed, which may provide valuable insights for further optimization. </div>
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<name sortKey="Li, Wenxin" sort="Li, Wenxin" uniqKey="Li W" first="Wenxin" last="Li">Wenxin Li</name>
<name sortKey="Liu, Xinyong" sort="Liu, Xinyong" uniqKey="Liu X" first="Xinyong" last="Liu">Xinyong Liu</name>
<name sortKey="Zhan, Peng" sort="Zhan, Peng" uniqKey="Zhan P" first="Peng" last="Zhan">Peng Zhan</name>
</country>
<country name="Belgique"><noRegion><name sortKey="Daelemans, Dirk" sort="Daelemans, Dirk" uniqKey="Daelemans D" first="Dirk" last="Daelemans">Dirk Daelemans</name>
</noRegion>
<name sortKey="De Clercq, Erik" sort="De Clercq, Erik" uniqKey="De Clercq E" first="Erik" last="De Clercq">Erik De Clercq</name>
<name sortKey="Pannecouque, Christophe" sort="Pannecouque, Christophe" uniqKey="Pannecouque C" first="Christophe" last="Pannecouque">Christophe Pannecouque</name>
</country>
</tree>
</affiliations>
</record>

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{{Explor lien
   |wiki=    Sante
   |area=    SrasV1
   |flux=    Main
   |étape=   Exploration
   |type=    RBID
   |clé=     pubmed:26994843
   |texte=   Design, synthesis and evaluation of novel HIV-1 NNRTIs with dual structural conformations targeting the entrance channel of the NNRTI binding pocket.
}}

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Serveur d'exploration SRAS

Design, synthesis and evaluation of novel HIV-1 NNRTIs with dual structural conformations targeting the entrance channel of the NNRTI binding pocket.

Design, synthesis and evaluation of novel HIV-1 NNRTIs with dual structural conformations targeting the entrance channel of the NNRTI binding pocket.

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	Serveur d'exploration SRAS
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