Design, synthesis and biological evaluation of piperazino-enaminones as novel suppressants of pro-Inflammatory cytokines

Ola M. Ghoneim, Ashley Bill, Jyothi Dhuguru, Doreen E. Szollosi, Ivan O. Edafiogho

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
JournalBioorganic and Medicinal Chemistry
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Cytokines
Interleukin-6
Tumor Necrosis Factor-alpha
Amination
Macrophages
Bioactivity
Scaffolds
Lipopolysaccharides
Asthma
Enzyme-Linked Immunosorbent Assay
Tissue
Wounds and Injuries
Infection
Cyclohexane

Keywords

  • Cytokines
  • Design
  • Inflammation
  • Pro-inflammatory
  • Synthesis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Design, synthesis and biological evaluation of piperazino-enaminones as novel suppressants of pro-Inflammatory cytokines. / Ghoneim, Ola M.; Bill, Ashley; Dhuguru, Jyothi; Szollosi, Doreen E.; Edafiogho, Ivan O.

In: Bioorganic and Medicinal Chemistry, 01.01.2018.

Research output: Contribution to journalArticle

Ghoneim, Ola M. ; Bill, Ashley ; Dhuguru, Jyothi ; Szollosi, Doreen E. ; Edafiogho, Ivan O. / Design, synthesis and biological evaluation of piperazino-enaminones as novel suppressants of pro-Inflammatory cytokines. In: Bioorganic and Medicinal Chemistry. 2018.
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