A novel anti-tumor agent, Ln(III) 2-thioacetate benzothiazole induces anti-angiogenic effect and cell death in cancer cell lines

Eur J Med Chem. 2012 May:51:99-109. doi: 10.1016/j.ejmech.2012.02.025. Epub 2012 Feb 21.

Abstract

New complexes with a potent DNA-binding anti-tumor agent, europium(III)- and terbium(III)-2-thioacetate benzothiazole were synthesized and characterized. These complexes showed strong binding affinity to calf thymus DNA using fluorometric and electronic absorption spectroscopy. The synthesized complexes resulted in inhibition of proliferation of EAC cells and ascites formation. Their anti-tumor effect was found to be through anti-angiogenic activity as was evident by the reduction of microvessel density and down-regulation of VEGF receptor type-2 (Flk-1). It was found that EAC cells had distinct DNA fragmentation patterns analyzed by capillary electrophoresis in the treated animals. Moreover, the synthesized complexes exhibited significant cytotoxic activity against HepG2 and MCF7 cell lines. Furthermore, complexes showed a potent anti-bacterial activity against two pathogenic bacteria Escherichia coli and Salmonella.

MeSH terms

  • Angiogenesis Inhibitors / chemistry
  • Angiogenesis Inhibitors / metabolism
  • Angiogenesis Inhibitors / pharmacology*
  • Angiogenesis Inhibitors / therapeutic use
  • Animals
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / metabolism
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Benzothiazoles / chemistry*
  • Carcinoma, Ehrlich Tumor / blood supply
  • Carcinoma, Ehrlich Tumor / pathology
  • Cell Death / drug effects
  • Cell Line, Tumor
  • DNA / metabolism
  • DNA Fragmentation / drug effects
  • Escherichia coli / drug effects
  • Europium / chemistry*
  • Female
  • Humans
  • Mice
  • Neovascularization, Pathologic / drug therapy*
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / metabolism
  • Organometallic Compounds / pharmacology*
  • Organometallic Compounds / therapeutic use
  • Salmonella / drug effects
  • Terbium / chemistry*
  • Tumor Burden / drug effects

Substances

  • Angiogenesis Inhibitors
  • Anti-Bacterial Agents
  • Antineoplastic Agents
  • Benzothiazoles
  • Organometallic Compounds
  • Terbium
  • Europium
  • DNA
  • calf thymus DNA
  • benzothiazole