1-ethyl-3-(6-methylphenanthridine-8-il) urea modulates TLR3/9 activation and induces selective pro-inflammatory cytokine expression in vitro

Bioorg Med Chem Lett. 2017 Apr 1;27(7):1530-1537. doi: 10.1016/j.bmcl.2017.02.048. Epub 2017 Feb 20.

Abstract

We have previously demonstrated the nucleic acid binding capacity of phenanthridine derivatives (PHTs). Because nucleic acids are potent inducers of innate immune response through Toll-like receptors (TLRs), and because PTHs bear a structural resemblance to commonly used synthetic ligands for TLR7/8, we hypothesized that PHTs could modulate/activate immune response. We found that compound M199 induces secretion of IL-6, IL-8 and TNFα in human PBMCs and inhibits TLR3/9 activation in different cellular systems (PBMCs, HEK293 and THP-1 cell lines).

Keywords: Cytokines; Immunomodulation; PBMCs; Phenanthridines; TLR.

MeSH terms

  • Cell Line
  • Down-Regulation
  • Humans
  • Immunologic Factors / pharmacology*
  • Intercalating Agents / pharmacology
  • Interferon-alpha / genetics
  • Interferon-alpha / metabolism
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism
  • Oligodeoxyribonucleotides / pharmacology
  • Phenanthridines / pharmacology*
  • Signal Transduction
  • Toll-Like Receptor 3 / metabolism*
  • Toll-Like Receptor 9 / metabolism*
  • Tumor Necrosis Factor-alpha / metabolism
  • Urea / analogs & derivatives*
  • Urea / pharmacology*

Substances

  • 1-ethyl-3-(6-methylphenanthridine-8-yl)urea
  • CXCL8 protein, human
  • CpG ODN 2216
  • IL6 protein, human
  • Immunologic Factors
  • Intercalating Agents
  • Interferon-alpha
  • Interleukin-6
  • Interleukin-8
  • ODN2006
  • Oligodeoxyribonucleotides
  • Phenanthridines
  • TLR3 protein, human
  • TLR9 protein, human
  • Toll-Like Receptor 3
  • Toll-Like Receptor 9
  • Tumor Necrosis Factor-alpha
  • Urea