1-ethyl-3-(6-methylphenanthridine-8-il) urea modulates TLR3/9 activation and induces selective pro-inflammatory cytokine expression in vitro. Issue 7 (1st April 2017)

• Record Type: Journal Article
• Authors: Teofilović, Natalija Knežević; Bihi, Mahjoub; Stojković, Marijana Radić; Tumir, Lidija M.; Ester, Katja; Kralj, Marijeta; Majhen, Dragomira; Oršolić, Nada; Lepur, Adriana; Vrbanec, Damir; Markotić, Alemka; Dembić, Zlatko; Weber, Alexander N.R.; Piantanida, Ivo; Vugrek, Oliver; Diken, Mustafa; Knežević, Jelena
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 27:Issue 7(2017)
• Page Start: 1530
• Page End: 1537
• Publication Date: 2017-04-01
• Subjects: Phenanthridines -- TLR -- PBMCs -- Cytokines -- Immunomodulation; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2017.02.048
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: 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).