Design, synthesis and biological evaluation of novel piperazine derivatives as CCR5 antagonists.
Identifieur interne : 001200 ( PubMed/Checkpoint ); précédent : 001199; suivant : 001201Design, synthesis and biological evaluation of novel piperazine derivatives as CCR5 antagonists.
Auteurs : Tao Liu [République populaire de Chine] ; Zhiyong Weng ; Xiaowu Dong ; Linjie Chen ; Ling Ma ; Shan Cen ; Naiming Zhou ; Yongzhou HuSource :
- PloS one [ 1932-6203 ] ; 2013.
Descripteurs français
- KwdFr :
- Agents antiVIH (pharmacologie), Agents antiVIH (synthèse chimique), Antagonistes des récepteurs CCR5, Cellules HEK293, Concentration inhibitrice 50, Conception de médicament, Dosage biologique, Expression des gènes, Fusion cellulaire, Gènes rapporteurs, Humains, Luciferases, Pipérazines (pharmacologie), Pipérazines (synthèse chimique), Protéine d'enveloppe gp120 du VIH (génétique), Protéine d'enveloppe gp120 du VIH (métabolisme), Relation structure-activité, Récepteurs CCR5 (métabolisme), Survie cellulaire (), VIH-1 (Virus de l'Immunodéficience Humaine de type 1) (), VIH-1 (Virus de l'Immunodéficience Humaine de type 1) (croissance et développement).
- MESH :
- croissance et développement : VIH-1 (Virus de l'Immunodéficience Humaine de type 1).
- génétique : Protéine d'enveloppe gp120 du VIH.
- métabolisme : Protéine d'enveloppe gp120 du VIH, Récepteurs CCR5.
- pharmacologie : Agents antiVIH, Pipérazines.
- synthèse chimique : Agents antiVIH, Pipérazines.
- Antagonistes des récepteurs CCR5, Cellules HEK293, Concentration inhibitrice 50, Conception de médicament, Dosage biologique, Expression des gènes, Fusion cellulaire, Gènes rapporteurs, Humains, Luciferases, Relation structure-activité, Survie cellulaire, VIH-1 (Virus de l'Immunodéficience Humaine de type 1).
English descriptors
- KwdEn :
- Anti-HIV Agents (chemical synthesis), Anti-HIV Agents (pharmacology), Biological Assay, CCR5 Receptor Antagonists, CD4 Antigens (genetics), CD4 Antigens (metabolism), Cell Fusion, Cell Survival (drug effects), Drug Design, Gene Expression, Genes, Reporter, HEK293 Cells, HIV Envelope Protein gp120 (genetics), HIV Envelope Protein gp120 (metabolism), HIV-1 (drug effects), HIV-1 (growth & development), Humans, Inhibitory Concentration 50, Luciferases, Piperazines (chemical synthesis), Piperazines (pharmacology), Receptors, CCR5 (metabolism), Structure-Activity Relationship.
- MESH :
- chemical , chemical synthesis : Anti-HIV Agents, Piperazines.
- chemical , genetics : CD4 Antigens, HIV Envelope Protein gp120.
- chemical , metabolism : CD4 Antigens, HIV Envelope Protein gp120, Receptors, CCR5.
- chemical , pharmacology : Anti-HIV Agents, Piperazines.
- drug effects : Cell Survival, HIV-1.
- growth & development : HIV-1.
- Biological Assay, CCR5 Receptor Antagonists, Cell Fusion, Drug Design, Gene Expression, Genes, Reporter, HEK293 Cells, Humans, Inhibitory Concentration 50, Luciferases, Structure-Activity Relationship.
Abstract
By using a fragment-assembly strategy and bioisosteric-replacement principle, a series of novel piperazine derivatives were designed, synthesized, and evaluated for their cellular target-effector fusion activities and in vitro antiviral activities against HIV-1. Preliminary structure-activity relationships (SARs) of target compounds were concluded in this study, and five compounds were found to exhibited medium to potent CCR5 fusion activities with IC(50) values in low micromolar level. Among evaluated compounds, 23 h was found to be a CCR5 antagonist with an IC(50) value of 6.29 µM and an anti-HIV-1 inhibitor with an IC(50) value of 0.44 µM.
DOI: 10.1371/journal.pone.0053636
PubMed: 23308267
Affiliations:
Links toward previous steps (curation, corpus...)
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pubmed:23308267Le document en format XML
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<front><div type="abstract" xml:lang="en">By using a fragment-assembly strategy and bioisosteric-replacement principle, a series of novel piperazine derivatives were designed, synthesized, and evaluated for their cellular target-effector fusion activities and in vitro antiviral activities against HIV-1. Preliminary structure-activity relationships (SARs) of target compounds were concluded in this study, and five compounds were found to exhibited medium to potent CCR5 fusion activities with IC(50) values in low micromolar level. Among evaluated compounds, 23 h was found to be a CCR5 antagonist with an IC(50) value of 6.29 µM and an anti-HIV-1 inhibitor with an IC(50) value of 0.44 µM.</div>
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<Reference><Citation>Antimicrob Agents Chemother. 2005 Aug;49(8):3474-82</Citation>
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<affiliations><list><country><li>République populaire de Chine</li>
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<name sortKey="Dong, Xiaowu" sort="Dong, Xiaowu" uniqKey="Dong X" first="Xiaowu" last="Dong">Xiaowu Dong</name>
<name sortKey="Hu, Yongzhou" sort="Hu, Yongzhou" uniqKey="Hu Y" first="Yongzhou" last="Hu">Yongzhou Hu</name>
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