Pt(II) complexes with bidentate and tridentate pyrazolyl-containing chelators: synthesis, structural characterization and biological studies

Dalton Trans. 2011 Jun 7;40(21):5781-92. doi: 10.1039/c0dt01785j. Epub 2011 Apr 21.

Abstract

A series of four Pt(II) complexes anchored by bidentate or tridentate pyrazolyl-alkylamine chelators bearing different substituents at the azolyl rings has been prepared with the aim to assess their interest in the design of novel anticancer drugs. All complexes have been fully characterized by classical analytical methods and three of them were characterized also by X-ray diffraction analysis. Their solution behavior, together with lipophilicity measurements, cell uptake, antiproliferative properties, DNA interaction have been evaluated. Albeit all the complexes were less active than cisplatin on ovarian carcinoma A2780 cell line, greatly retained their activity in the cisplatin-resistant A2780cisR cell line and presented a lower resistance factor compared to cisplatin. Moreover, the Pt(II) complexes under investigation were less prone to undergo deactivation by glutathione, believed to be the major cellular target of cisplatin that inactivates the drug by binding to it irreversibly.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Chelating Agents / chemistry*
  • Cisplatin / chemistry
  • Cisplatin / toxicity
  • Coordination Complexes / chemical synthesis*
  • Coordination Complexes / chemistry
  • Coordination Complexes / toxicity
  • Crystallography, X-Ray
  • DNA Damage
  • Drug Resistance, Neoplasm / drug effects
  • Humans
  • Molecular Conformation
  • Platinum / chemistry*
  • Pyrazoles / chemistry*

Substances

  • Chelating Agents
  • Coordination Complexes
  • Pyrazoles
  • pyrazole
  • Platinum
  • Cisplatin