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.
Natalija Knežević Teofilović  1 ,  Mahjoub Bihi  2 ,  Marijana Radić Stojković  1 ,  Lidija M Tumir  1 ,  Katja Ester  1 ,  Marijeta Kralj  1 ,  Dragomira Majhen  1 ,  Nada Oršolić  3 ,  Adriana Lepur  1 ,  Damir Vrbanec  4 ,  Alemka Markotić  5 ,  Zlatko Dembić  6 ,  Alexander N R Weber  7 ,  Ivo Piantanida  1 ,  Oliver Vugrek  1 ,  Mustafa Diken  8 ,  Jelena Knežević  9
Affiliations
  • 1. Ruđer Bošković Institute, Zagreb, Croatia.
  • 2. Biontech AG, Mainz, Germany.
  • 3. Faculty of Natural Science, Zagreb, Croatia.
  • 4. Department of Medical Oncology, University Hospital Center Zagreb, Croatia.
  • 5. University Hospital for Infectious Diseases "Dr. Fran Mihaljevic", Zagreb, Croatia.
  • 6. Department of Oral Biology, Faculty of Dentistry, University of Oslo, Norway.
  • 7. University of Tübingen, Department of Immunology, Germany.
  • 8. TRON-Translational Oncology at the University Medical Center of Johannes Gutenberg University GmbH, Mainz, Germany.
  • 9. Ruđer Bošković Institute, Zagreb, Croatia. Electronic address: [email protected].
PMID: 28254484 DOI: 10.1016/j.bmcl.2017.02.048
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.
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