trans-thionate derivatives of Pt(II) and Pd(II) with water-soluble phosphane PTA and DAPTA ligands: antiproliferative activity against human ovarian cancer cell lines

Inorg Chem. 2013 Jun 3;52(11):6635-47. doi: 10.1021/ic4006746. Epub 2013 May 21.

Abstract

A series of PTA and DAPTA platinum(II) and palladium(II) thionate complexes of the type trans-[M(SN)2P2] were prepared from the reaction of cis-[MCl2P2] [M = Pt, Pd; P = PTA (1,3,5-triaza-7-phosphaadamantane), DAPTA (3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane)] with the in situ generated sodium salts of the heterocyclic thiones S-m-methylpyrimidine-2-thione, S-4,6-dimethylpyrimidine-2-thione, S-4,6-dihydroxypyrimidine-2-thione, benzothiazole-2-thione, benzoxazole-2-thione, S-1,3,4,-thiadiazole-2-thione, S-4,5-H-thiazolan-2-thione, and S-pyrimidine-4(1H)-one-2-thione. The X-ray structures of six of the compounds confirm the trans disposition and, only in the case of [Pd2Cl2(S-pyrimidine-4(1H)-one-2-thionate)2(PTA)2], a dinuclear structure with a Pd-Pd distance of 3.0265(14)Å was observed. In vitro cytotoxicities against human ovarian cancer cell lines A2780 and A2780cisR were evaluated for ten complexes showing a high inhibition of cellular growth with a comparable inhibitory potency (IC50) against A2780 cells to that of cisplatin. Notably, the compounds also show significant (up to 7-fold higher) activity in cisplatin-resistant A2780cisR cell lines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adamantane / analogs & derivatives*
  • Adamantane / chemistry
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Bridged Bicyclo Compounds, Heterocyclic / chemistry*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Crystallography, X-Ray
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Ligands
  • Models, Molecular
  • Molecular Structure
  • Organometallic Compounds / chemical synthesis
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / pharmacology*
  • Organophosphorus Compounds / chemistry*
  • Palladium / chemistry
  • Platinum / chemistry
  • Solubility
  • Structure-Activity Relationship
  • Sulfhydryl Compounds / chemistry
  • Water / chemistry

Substances

  • 1,3,5-triaza-7-phosphaadamantane
  • 3,7-triaza-5-phosphabicyclo(3.3.1)nonane
  • Antineoplastic Agents
  • Bridged Bicyclo Compounds, Heterocyclic
  • Ligands
  • Organometallic Compounds
  • Organophosphorus Compounds
  • Sulfhydryl Compounds
  • Water
  • Platinum
  • Palladium
  • Adamantane