Ligand/PTC-free intramolecular Heck reaction: synthesis of pyrroloquinoxalines and their evaluation against PDE4/luciferase/oral cancer cell growth in vitro and zebrafish in vivo

Org Biomol Chem. 2013 Oct 21;11(39):6680-5. doi: 10.1039/c3ob41504j. Epub 2013 Aug 29.

Abstract

A series of 1,3-disubstituted pyrrolo[2,3-b]quinoxalines has been designed for the potential inhibition of PDE4 without inhibiting luciferase. A ligand/PTC (phase transfer catalyst) free intramolecular Heck cyclization strategy was used to prepare these compounds, some of which showed significant inhibition of PDE4B (IC50≈ 5-14 μM) and growth inhibition of oral cancer cells (CAL 27) but not inhibition of luciferase in vitro. They also showed acceptable safety profiles but no apoptosis in zebrafish embryos.

MeSH terms

  • Animals
  • Binding Sites
  • Catalysis
  • Cell Proliferation / drug effects
  • Embryo, Nonmammalian / drug effects
  • Enzyme Activation / drug effects
  • Humans
  • Ligands
  • Luciferases / metabolism
  • Molecular Structure
  • Mouth Neoplasms / drug therapy*
  • Phosphodiesterase 4 Inhibitors / chemical synthesis*
  • Phosphodiesterase 4 Inhibitors / chemistry
  • Phosphodiesterase 4 Inhibitors / pharmacology*
  • Quinoxalines / chemical synthesis*
  • Quinoxalines / chemistry
  • Quinoxalines / pharmacology*
  • Zebrafish / embryology

Substances

  • Ligands
  • Phosphodiesterase 4 Inhibitors
  • Quinoxalines
  • Luciferases