Synthesis, characterization and biological activity of trans-platinum(II) and trans-platinum(IV) complexes with 4-hydroxymethylpyridine

Chembiochem. 2005 Nov;6(11):2068-77. doi: 10.1002/cbic.200500108.

Abstract

The synthesis and chemical characterization of two new trans platinum complexes, trans-[PtCl(2)NH(3)(4-hydroxymethylpyridine)] (1) and trans-[PtCl(4)NH(3)(4-hydroxymethylpyridine)] (2) are described. Their ability to interact with 5'-GMP by themselves and in the presence of reducing agents in the case of trans-[PtCl(4)NH(3)(4-hydroxymethylpyridine)] were tested. Circular dichroism, electrophoretic mobility in agarose gel, and atomic force microscopy studies showed that the interaction of complex 1 with DNA is stronger than that of complex 2. Cytotoxicity tests against HL-60 tumor cells also showed higher activity for trans-[PtCl(2)NH(3)(4-hydroxymethylpyridine)] than for trans-[PtCl(4)NH(3)(4-hydroxymethylpyridine)]. Complex 1 presents similar behavior to cisplatin, but with a lower IC(50) at 24 h. Complex 1 also showed high apoptosis induction.

Publication types

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

MeSH terms

  • Apoptosis
  • Cell Line, Tumor
  • DNA / drug effects
  • DNA / metabolism
  • Guanosine Monophosphate / metabolism
  • HL-60 Cells
  • Humans
  • Magnetic Resonance Spectroscopy
  • Microscopy, Atomic Force
  • Organoplatinum Compounds / chemical synthesis*
  • Organoplatinum Compounds / chemistry
  • Organoplatinum Compounds / pharmacology*
  • Platinum Compounds / chemical synthesis*
  • Platinum Compounds / chemistry
  • Platinum Compounds / pharmacology*
  • Pyridines / chemical synthesis*
  • Pyridines / chemistry*
  • Pyridines / pharmacology*
  • Solubility
  • Water / chemistry

Substances

  • 4-hydroxymethylpyridine
  • Organoplatinum Compounds
  • Platinum Compounds
  • Pyridines
  • trans-PtCl(2)NH(3)(4-hydroxymethylpyridine)
  • Water
  • Guanosine Monophosphate
  • DNA