The Important Role of the Nuclearity, Rigidity, and Solubility of Phosphane Ligands in the Biological Activity of Gold(I) Complexes

Noora Svahn, Artur J. Moro, Catarina Roma-Rodrigues, Rakesh Puttreddy, Kari Rissanen, Pedro V. Baptista, Alexandra R. Fernandes, João Carlos Lima, Laura Rodríguez

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

A series of 4-ethynylaniline gold(I) complexes containing monophosphane (1,3,5-triaza-7-phosphaadamantane (pta; 2), 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane (3), and PR3 , with R=naphthyl (4), phenyl (5), and ethyl (6)) and diphosphane (bis(diphenylphosphino)acetylene (dppa; 7), trans-1,2-bis(diphenylphosphino)ethene (dppet; 8), 1,2-bis(diphenylphosphino)ethane (dppe; 9), and 1,3-bis(diphenylphosphino)propane (dppp; 10)) ligands have been synthesized and their efficiency against tumor cells evaluated. The cytotoxicity of complexes 2-10 was evaluated in human colorectal (HCT116) and ovarian (A2780) carcinoma as well as in normal human fibroblasts. All the complexes showed a higher antiproliferative effect in A2780 cells, with the cytotoxicity decreasing in the following order 5>6=9=10>8>2>4>7>3. Complex 4 stands out for its very high selectivity towards ovarian carcinoma cells (IC50 =2.3 μm) compared with colorectal carcinoma and normal human fibroblasts (IC50 >100 μm), which makes this complex very attractive for ovarian cancer therapy. Its cytotoxicity in these cells correlates with the induction of the apoptotic process and an increase of intracellular reactive oxygen species (ROS). The effects of the nuclearity, rigidity, and solubility of these complexes on their biological activity were also analyzed. X-ray crystal structure determination allowed the identification of short N-H⋅⋅⋅π contacts as the main driving forces for the three-dimensional packing in these molecules.

Original languageEnglish
Pages (from-to)14654-14667
Number of pages14
JournalChemistry-A European Journal
Volume24
Issue number55
DOIs
Publication statusPublished - 1 Oct 2018

Keywords

  • antitumor agents
  • apoptosis
  • biological activity
  • gold
  • X-ray diffraction

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