Design, synthesis and biological evaluation of piperazino-enaminones as novel suppressants of pro-Inflammatory cytokines
Copyright © 2018 Elsevier Ltd. All rights reserved..
Infection triggers the release of pro-inflammatory cytokines (TNF-alpha and IL-6). Over-production, however, cause tissue injury seen in severe asthma. The ability of enaminone E121 to reduce pro-inflammatory cytokines in our laboratory encouraged further examination of its structural scaffold. Piperazino-enaminones were designed by incorporating n-arylpiperazine motif into the aromatic enaminone. Four possible modifications were explored systematically. Synthesis was accomplished by amination of the corresponding methyl/ethyl 2,4-dioxo-6-(substituted)cyclohexane-carboxylate.. Sixteen novel compounds were synthesized. Biological activity was tested in J774 macrophages stimulated with lipopolysaccharides. The release of cytokines was measured via ELISA. Four compounds significantly suppressed TNF-alpha and IL-6 release in dose-dependent manner.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2018 |
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| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:26 |
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| Enthalten in: |
Bioorganic & medicinal chemistry - 26(2018), 14 vom: 07. Aug., Seite 3890-3898 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ghoneim, Ola M [VerfasserIn] |
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| Links: |
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| Themen: |
Aniline Compounds |
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| Anmerkungen: |
Date Completed 31.01.2019 Date Revised 31.01.2019 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bmc.2018.06.003 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM285476858 |
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| 520 | |a Copyright © 2018 Elsevier Ltd. All rights reserved. | ||
| 520 | |a Infection triggers the release of pro-inflammatory cytokines (TNF-alpha and IL-6). Over-production, however, cause tissue injury seen in severe asthma. The ability of enaminone E121 to reduce pro-inflammatory cytokines in our laboratory encouraged further examination of its structural scaffold. Piperazino-enaminones were designed by incorporating n-arylpiperazine motif into the aromatic enaminone. Four possible modifications were explored systematically. Synthesis was accomplished by amination of the corresponding methyl/ethyl 2,4-dioxo-6-(substituted)cyclohexane-carboxylate.. Sixteen novel compounds were synthesized. Biological activity was tested in J774 macrophages stimulated with lipopolysaccharides. The release of cytokines was measured via ELISA. Four compounds significantly suppressed TNF-alpha and IL-6 release in dose-dependent manner | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Cytokines | |
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| 650 | 4 | |a Pro-inflammatory | |
| 650 | 4 | |a Synthesis | |
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| 650 | 7 | |a Cyclohexanecarboxylic Acids |2 NLM | |
| 650 | 7 | |a Cytokines |2 NLM | |
| 650 | 7 | |a E 121 compound |2 NLM | |
| 650 | 7 | |a Lipopolysaccharides |2 NLM | |
| 650 | 7 | |a Piperazines |2 NLM | |
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| 700 | 1 | |a Dhuguru, Jyothi |e verfasserin |4 aut | |
| 700 | 1 | |a Szollosi, Doreen E |e verfasserin |4 aut | |
| 700 | 1 | |a Edafiogho, Ivan O |e verfasserin |4 aut | |
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