Structure-activity relationship study of a series of novel oxazolidinone derivatives as IL-6 signaling blockers

Bioorg Med Chem Lett. 2016 Feb 15;26(4):1282-6. doi: 10.1016/j.bmcl.2016.01.016. Epub 2016 Jan 9.

Abstract

A series of oxazolidinone and indole derivatives were synthesized and evaluated as IL-6 signaling blockers by measuring the effects of these compounds on IL-6-induced luciferase expression in human hepatocarcinoma HepG2 cells transfected with p-STAT3-Luc. Among different compounds screened, compound 4d was emerged as the most potent IL-6 signaling blockers with IC50 value of 5.9 μM which was much better than (+)-Madindoline A (IC50=21 μM), a known inhibitor of IL-6.

Keywords: IL-6 antagonists; IL-6 signaling inhibitor; Oxazolidinone; Rheumatoid arthritis; STAT3; gp130.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Bridged Bicyclo Compounds, Heterocyclic / chemistry
  • Crystallography, X-Ray
  • Hep G2 Cells
  • Humans
  • Indoles / chemistry
  • Inhibitory Concentration 50
  • Interleukin-6 / antagonists & inhibitors
  • Interleukin-6 / metabolism*
  • Molecular Docking Simulation
  • Oxazolidinones / chemical synthesis
  • Oxazolidinones / chemistry*
  • Oxazolidinones / pharmacology
  • Protein Structure, Tertiary
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction / drug effects*
  • Structure-Activity Relationship

Substances

  • Bridged Bicyclo Compounds, Heterocyclic
  • Indoles
  • Interleukin-6
  • Oxazolidinones
  • STAT3 Transcription Factor
  • madindoline A