Mono-carboxylated diaminedichloridoplatinum(IV) complexes--selective synthesis, characterization, and cytotoxicity

Dalton Trans. 2011 Aug 28;40(32):8187-92. doi: 10.1039/c1dt10301f. Epub 2011 Jul 11.

Abstract

(OC-6-43)-Dichlorido(N,N-dimethyl-ethane-1,2-diamine)dihydroxidoplatinum(IV) could selectively be mono-carboxylated with succinic anhydride based on the steric hindrance caused by the two methyl groups of the equatorial ligand. Subsequent esterification of the uncoordinated carboxylic acid with alcohols of different lengths (methanol, butanol, hexanol and octanol) afforded the corresponding esters. The synthesized complexes were characterized in detail by elemental analysis, ESI-MS, multinuclear ((1)H, (13)C, (15)N and (195)Pt) NMR spectroscopy and in two cases by X-ray crystallography. Cytotoxicity of novel platinum(IV) compounds was investigated in four human cancer cell lines (CH1, A549, SW480 and SK-OV-3). Remarkably, the most lipophilic complexes showed IC(50) values down to the low micromolar or even nanomolar range.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Chlorides / chemical synthesis
  • Chlorides / chemistry
  • Chlorides / pharmacology
  • Crystallography, X-Ray
  • Diamines / chemical synthesis
  • Diamines / chemistry*
  • Diamines / pharmacology*
  • Drug Screening Assays, Antitumor
  • Humans
  • Models, Molecular
  • Neoplasms / drug therapy
  • Organoplatinum Compounds / chemical synthesis
  • Organoplatinum Compounds / chemistry*
  • Organoplatinum Compounds / pharmacology*

Substances

  • Antineoplastic Agents
  • Chlorides
  • Diamines
  • Organoplatinum Compounds