Synthesis, characterization, DNA binding studies and in vitro cytotoxicity of platinum(II)-dihalogenido complexes containing bidentate chelating N-donor ligands

Abstract

Platinum(II) complexes, [Pt(L_x)X₂] (1–6), where X = Br or I and L_x = 2,2′-bipyridine or 1,10-phenanthroline derivatives (5,5′-dimethyl-2,2′-bipyridine (5-Mebpy), 4,4′-dimethyl-2,2′-bipyridine (4-Mebpy), and 5-amino-1,10-phenanthroline (5-NH₂phen)) were prepared. The complexes were characterized by the elemental analysis, mass spectrometry, infrared, and multinuclear (¹H, ¹³C and ¹⁹⁵Pt) 1-D and 2-D NMR spectroscopies, and by single-crystal X-ray analysis of [Pt(4-Mebpy)I₂] (4). All the platinum(II) complexes (1–6) were evaluated for in vitro cytotoxicity against human cancer cell lines A2780 and A2780R, and against non-malignant MRC5 cell line. All the complexes were nontoxic up to the 50 μM concentration, although they were found to readily bind to calf-thymus DNA (CT-DNA), as determined by spectrophotometric titration (K_b ≈ 10⁷ M⁻¹) and ethidium bromide displacement assay.

Keywords:

• Platinum(II) complexes
• 2,2′-bipyridine derivatives
• 1,10-phenanthroline derivatives
• in vitro cytotoxicity
• CT-DNA
• crystal structure

Acknowledgements

The authors gratefully acknowledge the support by the project LO1305 of the Ministry of Education, Youth and Sports of the Czech Republic. The X-ray part of the work was realized in X-ray Diffraction and BioSAXS Core Facility of CEITEC – Central European Institute of Technology under CEITEC – open access project, ID number LM2011020, funded by the Ministry of Education, Youth and Sports of the Czech Republic. The authors also thank Dr Jana Gáliková and Dr Alena Klanicová for performing FT-IR experiments, Dr Bohuslav Drahoš for ESI MS experiments, and Ms Kateřina Kubešová for cytotoxicity testing.