Non-classical anticancer agents: synthesis and biological evaluation of zinc(II) heteroleptic complexes

Dalton Trans. 2010 May 7;39(17):4205-12. doi: 10.1039/b922101h. Epub 2010 Mar 24.

Abstract

New heteroleptic complexes (1-8) containing Zn(II) ion coordinated to an N,N-chelating ligand (the 4,4'-dinonyl-2,2'-bipyridine, bpy-9) and to diketonates L such as tropoloids (Tropolone and Hinokitiol) or 1-phenyl-3-methyl-4-R-5-pyrazolones have been synthesized by using different stoichiometric ratio with respect to the L ancillary ligand. The molecular structure of the bis-tropolonate derivative [(bpy-9)Zn(L)(2)] 5 has been determined by single-crystal X-ray diffraction. The antitumour activity of all Zn(II) complexes was tested in vitro against three different human prostate cancer cells: DU145, LNCaP and PC-3. Moreover, their effect on cell survival signalling and/or inhibitors of the PC-3 cell cycle have been analyzed. The results indicate that 1-8 exhibit strong cytotoxic activity against all cell lines affecting key molecules such as p-AKT and p21 waf, involved in the cell proliferation and/or arrest. Zinc(II) is thus a promising alternative to Pt(II) ion in the design of new, better performing antitumour agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2,2'-Dipyridyl / chemistry
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Coordination Complexes / chemical synthesis*
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacology
  • Crystallography, X-Ray
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Drug Screening Assays, Antitumor
  • Humans
  • Molecular Conformation
  • Proto-Oncogene Proteins c-akt / metabolism
  • Zinc / chemistry*

Substances

  • Antineoplastic Agents
  • Coordination Complexes
  • Cyclin-Dependent Kinase Inhibitor p21
  • 2,2'-Dipyridyl
  • Proto-Oncogene Proteins c-akt
  • Zinc