Novel platinum(II) and palladium(II) complexes with cyclin-dependent kinase inhibitors: synthesis, characterization and antitumour activity

Bioorg Med Chem. 2006 Jan 15;14(2):479-91. doi: 10.1016/j.bmc.2005.08.033. Epub 2005 Sep 28.

Abstract

The Pt(II) and Pd(II) complexes of the types cis-[Pt(L(1))(2)Cl(2)].H(2)O (1), cis-[Pt(L(2))(2)Cl(2)].3H(2)O (2), trans-[Pd(L(1))(2)Cl(2)].H(2)O (3), trans-[Pd(L(2))(2)Cl(2)].H(2)O (4), trans-[Pd(L(3))(2)Cl(2)].2DMF (5) and trans-[Pd(L(4))(2)Cl(2)].2DMF (6) (L(1)-L(4)=cyclin-dependent kinase inhibitors derived from 6-benzylamino-9-isopropylpurine) have been prepared and characterized. The complexes have been studied by elemental analyses, conductivity measurements, ES+ MS, FT-IR, (1)H, (13)C and (195)Pt NMR spectra, differential scanning calorimetry and thermogravimetric analysis. The molecular structures of L(1), trans-[Pd(L(3))(2)Cl(2)].2DMF (5) and trans-[Pd(L(4))(2)Cl(2)].2DMF (6) have been determined by single crystal X-ray analysis. The complexes have been tested in vitro due to their presumable anticancer activity against the following human cancer cell lines: K-562, MCF7, G-361 and HOS. Satisfying results were obtained for the complex 1 with IC(50) values of 6 microM acquired against G-361 as well as against HOS cell lines. The lowest values of IC(50) were achieved for the complexes 3 and 4 against MCF 7 cell line with IC(50) 3 microM(for 3) and also 3 microM (for 4).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Calorimetry, Differential Scanning
  • Crystallography, X-Ray
  • Cyclin-Dependent Kinases / antagonists & inhibitors*
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Palladium / chemistry*
  • Palladium / pharmacology
  • Platinum Compounds / chemical synthesis
  • Platinum Compounds / chemistry*
  • Platinum Compounds / pharmacology
  • Spectrometry, Mass, Electrospray Ionization
  • Spectrophotometry, Infrared

Substances

  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Platinum Compounds
  • Palladium
  • Cyclin-Dependent Kinases