Gold(I) complexes with alkylated PTA (1,3,5-triaza-7-phosphaadamantane) phosphanes as anticancer metallodrugs

Eur J Med Chem. 2014 May 22:79:164-72. doi: 10.1016/j.ejmech.2014.04.001. Epub 2014 Apr 1.

Abstract

New stable thiolate gold(I) derivatives containing the alkylated phosphanes [PTA-CH2Ph]Br and [PTA-CH2COOMe]Br derived from 1,3,5-triaza-7-phosphaadamantane (PTA) have been prepared by different routes of synthesis. By the use of basic media to deprotonate the corresponding thiol in the former and by transmetallation reactions from tin (IV) complexes, in the later, thus avoiding side reactions on the phosphane. Strong antiproliferative effects are observed for most of the compounds, including the chloro- and bromo precursors with the series of phosphanes derived from PTA, in human colon cancer cell lines (Caco-2, PD7 and TC7 clones). Apoptosis-induced cell death is found for all compounds, being the thiolate derivatives with [PTA-CH2Ph]Br the most effective, as shown by an annexin-V/propidium iodide double-staining assay.

Keywords: Antitumor properties; Gold; PTA; Thiolate; Water soluble.

MeSH terms

  • Adamantane / analogs & derivatives*
  • Adamantane / chemistry
  • Alkylation
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Caco-2 Cells
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Molecular Structure
  • Organogold Compounds / chemical synthesis
  • Organogold Compounds / chemistry
  • Organogold Compounds / pharmacology*
  • Organophosphorus Compounds / chemistry*
  • Phosphines / chemistry*
  • Structure-Activity Relationship

Substances

  • 1,3,5-triaza-7-phosphaadamantane
  • Antineoplastic Agents
  • Organogold Compounds
  • Organophosphorus Compounds
  • Phosphines
  • phosphine
  • Adamantane