@article {16173, title = {The Important Role of the Nuclearity, Rigidity, and Solubility of Phosphane Ligands in the Biological Activity of Gold(I) Complexes}, journal = {Chemistry}, volume = {24}, year = {2018}, note = {

Svahn, NooraMoro, Artur J
Roma-Rodrigues, Catarina
Puttreddy, Rakesh
Rissanen, Kari
Baptista, Pedro V
Fernandes, Alexandra R
Lima, Joao Carlos
Rodriguez, Laura
eng
CTQ2016-76120-P/Ministerio de Economia, Industria y Competitividad, Gobierno de Espana
UID/QUI/50006/2013/Fundacao para a Ciencia e a Tecnologia
UID/Multi/04378/2013/Fundacao para a Ciencia e a Tecnologia
298817/Academy of Finland
Germany
Chemistry. 2018 Oct 1;24(55):14654-14667. doi: 10.1002/chem.201802547. Epub 2018 Sep 3.

}, month = {2018}, pages = {14654-14667}, 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 mum) compared with colorectal carcinoma and normal human fibroblasts (IC50 \>100 mum), 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-Hpi contacts as the main driving forces for the three-dimensional packing in these molecules.

}, keywords = {Antineoplastic Agents/chemical synthesis/*chemistry/pharmacology, antitumor agents, Apoptosis, bcl-2-Associated X Protein/metabolism, biological activity, Cell Line, Cell Survival/drug effects, Coordination Complexes/chemical synthesis/*chemistry/pharmacology, Crystallography, X-Ray, Gold, Gold/*chemistry, HCT116 Cells, Humans, Ligands, Membrane Potential, Mitochondrial/drug effects, Molecular Conformation, Phosphines/*chemistry, Proto-Oncogene Proteins c-bcl-2/metabolism, Quantum Theory, Reactive Oxygen Species/metabolism, Solubility, Structure-Activity Relationship, X-ray diffraction}, isbn = {1521-3765 (Electronic)0947-6539 (Linking) }, url = {https://www.ncbi.nlm.nih.gov/pubmed/30063270}, author = {Svahn, N. and Moro, A. J. and Roma-Rodrigues, C. and Puttreddy, R. and Rissanen, K. and P.V. Baptista and Fernandes, A. R. and J. C. Lima and Rodriguez, L} }