Concise synthesis of carbazole-1,4-quinones and evaluation of their antiproliferative activity against HCT-116 and HL-60 cells

Eur J Med Chem. 2016 Oct 4:121:561-577. doi: 10.1016/j.ejmech.2016.05.065. Epub 2016 Jun 3.

Abstract

We report a convenient synthesis of carbazole-1,4-quinone alkaloid koeniginequinones A and B using a tandem ring-closing metathesis with the dehydrogenation reaction sequence under an O2 atmosphere as an important step. Using this method, carbazole-1,4-quinones substituted at the 5-, 6-, 7-, and/or 8-positions have been synthesized. Moreover, 24 compounds, including koeniginequinones A and B, have been evaluated for their antiproliferative activity against HCT-116 and HL-60 cells, and the 6-nitro analog exhibited the most potent activity against both tumor cell types.

Keywords: Antiproliferative activity; Carbazole-1,4-quinone; Koeniginequinone A; Koeniginequinone B.

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Carbazoles / chemical synthesis*
  • Carbazoles / chemistry
  • Carbazoles / pharmacology*
  • Cell Proliferation / drug effects
  • Chemistry Techniques, Synthetic
  • HCT116 Cells
  • HL-60 Cells
  • Humans
  • Quinones / chemical synthesis*
  • Quinones / chemistry
  • Quinones / pharmacology*

Substances

  • Antineoplastic Agents
  • Carbazoles
  • Quinones