Gram-scale synthesis of FICZ, a photoreactive endogenous ligand of the aryl hydrocarbon receptor

Sci Rep. 2019 Jul 10;9(1):9982. doi: 10.1038/s41598-019-46374-7.

Abstract

Development of an efficient and scalable synthesis of 6-formylindolo[3,2-b]carbazole (FICZ), a naturally-occurring aryl hydrocarbon receptor (AhR) ligand, allowed its biological and physical properties to be studied. FICZ was shown to be the most potent among a series of 6-substituted indolo[3,2-b]carbazoles for activation of AhR in cells. Photostability studies of FICZ revealed a non-enzymatic mechanism for its conversion to a biologically active quinone. These results further support the hypothesis that FICZ is a light-dependent hormone that links sun exposure to regulation of biological pathways in peripheral tissues.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Carbazoles / chemical synthesis*
  • Carbazoles / chemistry
  • Carbazoles / pharmacology
  • Cell Line
  • Drug Stability
  • Humans
  • Ligands
  • Molecular Structure
  • Photochemical Processes
  • Receptors, Aryl Hydrocarbon / metabolism*

Substances

  • 6-formylindolo(3,2-b)carbazole
  • AHR protein, human
  • Basic Helix-Loop-Helix Transcription Factors
  • Carbazoles
  • Ligands
  • Receptors, Aryl Hydrocarbon