Synthesis and cytotoxicity of new platinum(IV) complexes of mixed carboxylates

J Inorg Biochem. 2003 Aug 1;96(2-3):339-45. doi: 10.1016/s0162-0134(03)00149-1.

Abstract

In order to develop new antitumor platinum(IV) complexes with highly tuned lipophilicity, a series of (diamine)Pt(IV) complexes of the formula [Pt(IV)(dach)L(3)L'] or [Pt(IV)(dach)L(2)L"(2)] (dach=trans-(+/-)-1,2-diaminocyclohexane; L=acetato, propionato; L'=acetato, propionato, valerato or pivalato; L"=trifluoroacetato) have been synthesized by electrophilic substitution of the tris(carboxylato)hydroxoplatinum(IV) complexes, [Pt(IV)(dach)L(3)OH] (L=acetato, propionato), with various carboxylic anhydrides such as acetic, trifluoroacetic, pivalic and valeric anhydrides. The present platinum(IV) complexes were fully characterized by means of elemental analyses, 1H NMR, mass and IR spectroscopies. The complexes 8 and 10, satisfying the appropriate range of lipophilicity (logP=0.18-1.54), exhibited high activity (ED(50), 5.1 and 1.3 microM, respectively) compared with other complexes, which implies that the lipophilicity is an important factor for the antitumor activity of this series of complexes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology
  • Carboxylic Acids / chemical synthesis
  • Carboxylic Acids / pharmacology
  • Cell Survival / drug effects
  • Crystallography, X-Ray
  • Guanosine Monophosphate / chemistry
  • Hydrophobic and Hydrophilic Interactions
  • Mice
  • Molecular Structure
  • Organometallic Compounds / chemical synthesis*
  • Organometallic Compounds / pharmacology
  • Platinum / chemistry*
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Carboxylic Acids
  • Organometallic Compounds
  • Platinum
  • Guanosine Monophosphate