Synthesis and biological evaluation of FICZ analogues as agonists of aryl hydrocarbon receptor

  • Bioorg Med Chem Lett. 2020 Mar 1;30(5):126959. doi: 10.1016/j.bmcl.2020.126959.
Hao Wu  1 ,  Binkai Liu  1 ,  Ka Yang  1 ,  Gabrielle N Winston-McPherson  1 ,  Eric D Leisten  1 ,  Chad M Vezina  2 ,  William A Ricke  3 ,  Richard E Peterson  1 ,  Weiping Tang  4
Affiliations
  • 1. School of Pharmacy, University of Wisconsin-Madison, 777 Highland Avenue, Madison, WI 53705, USA.
  • 2. Department of Comparative Biosciences, University of Wisconsin-Madison, School of Veterinary Medicine, Madison, WI 53706, USA; University of Wisconsin-Madison, O'Brien Urology Research Center, Madison, WI, USA.
  • 3. University of Wisconsin-Madison, O'Brien Urology Research Center, Madison, WI, USA; Department of Urology and Carbone Cancer Center, University of Wisconsin-Madison, School of Medicine and Public Health, Madison, WI 53705, USA.
  • 4. School of Pharmacy, University of Wisconsin-Madison, 777 Highland Avenue, Madison, WI 53705, USA; Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, WI 53706, USA. Electronic address: [email protected].
PMID: 31952965 DOI: 10.1016/j.bmcl.2020.126959
Abstract

The Aryl Hydrocarbon Receptor (AhR) is a ligand activated transcription factor involved in multiple biological processes including immune cell differentiation, intestinal function and inflammation. Based on the scaffold of naturally occurring AhR ligand 6-formylindolo (3,2-b) carbazole (FICZ, 2), a series of analogues has been designed, synthesized and evaluated by cell-based assays. The structure-activity relationships study has successfully led to the discovery of compound 11e with extremely potent activity.

Keywords
AhR; Benign prostatic hyperplasia; Carbazole; FICZ; Transcription factor.