Combining the platinum(ii) drug candidate kiteplatin with 1,10-phenanthroline analogues

Dalton Trans. 2018 Feb 13;47(7):2156-2163. doi: 10.1039/c7dt04108j.

Abstract

Platinum complexes of the type [Pt(PL)(AL)]2+ where PL is a derivative of 1,10-phenanthroline and AL is cis-1,4-diaminocyclohexane (1,4-dach), have been synthesised and characterised by ultraviolet spectroscopy, elemental microanalysis, nuclear magnetic resonance and X-ray crystallography. The calf-thymus DNA binding affinity of these complexes was determined by isothermal titration calorimetry, revealing higher DNA affinity than their 1S,2S-diaminocyclohexane analogues. In vitro cytotoxicity was assessed in eleven human cell lines, revealing unexpectedly low activity for the 1,4-dach complexes.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology*
  • Cattle
  • Cell Line, Tumor
  • DNA / metabolism
  • Humans
  • Organoplatinum Compounds / chemistry*
  • Organoplatinum Compounds / metabolism
  • Organoplatinum Compounds / pharmacology*
  • Phenanthrolines / chemistry*

Substances

  • Antineoplastic Agents
  • Organoplatinum Compounds
  • Phenanthrolines
  • platinum(II)(1,4-diazacycloheptane)dichloride
  • DNA
  • calf thymus DNA
  • 1,10-phenanthroline