Bis-intercalative dinuclear platinum(II) 6-phenyl-2,2'-bipyridine complexes exhibit enhanced DNA affinity but similar cytotoxicity compared to the mononuclear unit

J Biol Inorg Chem. 2003 Sep;8(7):761-9. doi: 10.1007/s00775-003-0477-0. Epub 2003 Jul 22.

Abstract

The interactions between a series of platinum complexes, including (pyridyl)(6-phenyl-2,2'-bipyridine)platinum(II) hexafluorophosphate (1), three dinuclear bis[(6-phenyl-2,2'-bipyridine)platinum(II)] complexes (2-4), and (4-aminopyridine)(4,6-diphenyl-2,2'-bipyridine)platinum(II) perchlorate (5) with DNA have been investigated. All Pt(II) complexes, except 5, were demonstrated to be DNA intercalators, based on viscosity measurements. Absorption and fluorescence titration results indicated that the addition of a phenyl ring to the 6-phenyl-2,2'-bipyridine ligand dramatically reduced the DNA binding of the Pt(II) complex 5. The dinuclear complexes 2-4 exhibited multiple binding modes of mono/bisintercalation and groove binding, as revealed by viscosity and fluorescence titration measurements. While complexes 2-4 bound to DNA with significantly enhanced affinities as compared to 1, compounds 1 and 2-4 showed similar IC(50) values against a panel of cancer cell lines. In addition, these complexes showed similar cellular uptakes. The results indicated that the cytotoxicity of these (6-phenyl-2,2'-bipyridine)platinum compounds may not be mediated through DNA binding but may involve interacting mechanisms with cellular components other than DNA.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • DNA / chemistry
  • DNA / metabolism*
  • Drug Screening Assays, Antitumor
  • Humans
  • Intercalating Agents / chemical synthesis
  • Intercalating Agents / pharmacology
  • Nucleic Acid Conformation / drug effects
  • Organoplatinum Compounds / chemical synthesis
  • Organoplatinum Compounds / pharmacology*
  • Pyridines / chemical synthesis
  • Pyridines / pharmacology*
  • Spectrum Analysis
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Intercalating Agents
  • Organoplatinum Compounds
  • Pyridines
  • platinum(II) 6-phenyl-2,2'-bipyridine
  • DNA