High cytotoxicity of dihalo-substituted 8-quinolinolato-lanthanides

Dalton Trans. 2011 Feb 28;40(8):1684-92. doi: 10.1039/c0dt01310b. Epub 2011 Jan 24.

Abstract

Three new lanthanide complexes with dihalo-substituted 8-quinolinol: [Gd(BrQ)(3)(H(2)O)(2)]·1.33EtOH·0.33H(2)O (1), [Dy(ClQ)(3)(H(2)O)(2)]·1.33EtOH·0.33H(2)O (2), [Er(ClQ)(3)(H(2)O)(2)]·1.33EtOH·0.33H(2)O (3) (H-BrQ = 5,7-dibromo-8-quinolinol, H-ClQ = 5,7-dichloro-8-quinolinol) have been synthesized and characterized by elemental analysis, IR, ESI-MS, single-crystal X-ray diffraction and TGA. The single-crystal X-ray diffraction analyses reveal that complexes 1-3 are mononuclear and isostructural. Each metal centre is coordinated by three dihalo-substituted 8-quinolinol and two aqua ligands. The in vitro cytotoxicity of dihalo-substituted 8-quinolinol and complexes 1-3 against liver cancer BEL7404 was evaluated. The IC(50) values of 1-3 to BEL7404 were 47.2 ± 2.6, 18.3 ± 1.0 and 31.5 ± 1.2 nM, respectively. The lanthanide complexes 1-3 exhibited significantly enhanced cytotoxicity vs. free substituted 8-quinolinol. The binding properties of dihalo-substituted 8-quinolinol and complexes 1 and 2 to DNA were investigated by UV-vis, fluorescence, CD spectroscopy and viscosity measurements, as well as agarose gel electrophoresis experiments. Both complexes 1 and 2 interact more strongly with DNA than the free quinolinol ligand. Intercalation is the most probable binding mode for both the complexes and the quinolinol ligands.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Cattle
  • Cell Death / drug effects
  • Cell Line
  • Circular Dichroism
  • Crystallography, X-Ray
  • Cytotoxins / chemical synthesis
  • Cytotoxins / chemistry
  • Cytotoxins / pharmacology
  • DNA / metabolism
  • Humans
  • Lanthanoid Series Elements / chemical synthesis
  • Lanthanoid Series Elements / chemistry*
  • Lanthanoid Series Elements / pharmacology*
  • Liver Neoplasms / drug therapy
  • Models, Molecular
  • Quinolines / chemical synthesis
  • Quinolines / chemistry*
  • Quinolines / pharmacology*
  • Spectrophotometry

Substances

  • Antineoplastic Agents
  • Cytotoxins
  • Lanthanoid Series Elements
  • Quinolines
  • DNA
  • calf thymus DNA