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

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

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: jknezev@irb.hr.
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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