The first ruthenium-based paullones: syntheses, X-ray diffraction structures, and spectroscopic and antiproliferative properties in vitro

Inorg Chem. 2007 Apr 30;46(9):3645-56. doi: 10.1021/ic070098j. Epub 2007 Apr 3.

Abstract

Two novel paullone derivatives, namely, 6-(alpha-picolylamino)-7,12-dihydroindolo[3,2-d][1]benzazepine (L1) and 9-bromo-6-(alpha-picolylamino)-7,12-dihydroindolo[3,2-d][1]benzazepine (L2), have been prepared. The reaction of cis-[RuCl2(DMSO)4] (DMSO=dimethyl sulfoxide) with L1 and L2 in a 1:1 molar ratio in dry ethanol at 50 degrees C afforded the complexes trans-[RuIICl2(DMSO)2L1] (1a) and trans-[RuIICl2(DMSO)2L2] (1b) in 26 and 30% yield, respectively. The reaction carried out from the same starting compounds in a 1:2 molar ratio at 75 degrees C led to the formation of [RuIICl(DMSO)(L1)2]Cl (2a) and [RuIICl(DMSO)(L2)2]Cl (2b) in 16 and 23% yield, correspondingly. The products were characterized by elemental analysis, one- and two-dimensional NMR spectroscopy, electrospray ionization mass spectrometry, IR spectroscopy, electronic spectra, cyclic voltammetry, and X-ray crystallography (L1, L2, 1a, and 2b). Complexes 2a and 2b exhibit remarkable antiproliferative activity in three human carcinoma cell lines, A549 (non-small cell lung carcinoma), CH1 (ovarian carcinoma), and SW480 (colon carcinoma). The novel complexes show an intercalative mode of interaction with DNA, which may render them attractive alternatives to metal compounds with a coordinative mode of interaction.

MeSH terms

  • Benzazepines / chemistry*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • DNA / chemistry
  • Electrons
  • Gases / chemistry
  • Humans
  • Indoles / chemistry*
  • Ligands
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Molecular Structure
  • Ruthenium Compounds / chemical synthesis*
  • Ruthenium Compounds / chemistry
  • Ruthenium Compounds / toxicity*
  • X-Ray Diffraction

Substances

  • Benzazepines
  • Gases
  • Indoles
  • Ligands
  • Ruthenium Compounds
  • DNA