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The important role of the nuclearity, rigidity, and solubility of phosphane ligands in the biological activity of gold(I) complexes

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A series of 4-ethynylaniline gold(I) complexes containing monophosphanes (1,3,5-triaza-7-phosphaadamantane, PTA, 2; 3,7-diacetyl-1,3,7-triaza-5-fosfabiciclo[3.3.1]nonane, 3; and PR3, being R = naphtyl, 4; phenyl, 5 and ethyl, 6) and diphosphanes (bis(diphenylphosphino)acetylene, dppa, 7; trans-diphenylphosphineethene, dppet, 8; 1,2-bis(diphenylphosphino)ethane, dppe, 9; 1,3-bis(diphenylphosphino)propane, dppp, 10) ligands was synthetized and their efficiency against tumor cells evaluated. The cytotoxicity of complexes 2-10 was evaluated in human colorectal (HCT116) and ovarian (A2780) carcinoma, to the effect on normal human fibroblasts. All the complexes showed a higher antiproliferative effect in A2780 cells, with the following order of cytotoxicity: 5 > 6 = 9 = 10 > 8 > 2 > 4 > 7 > 3. Complex 4 stands out for a very high selectivity towards ovarian carcinoma cells (IC50 2.3 M), compared to colorectal carcinoma and normal human fibroblasts (IC50 > 100 M), making 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 effect of the nuclearity, rigidity and solubility of the complexes on their biological activity was also analyzed. X-Ray crystal structures determination allowed the identification of short N-H··· contacts as the main driving forces for the 3D packing in these molecules.

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SVAHN, Noora, MORO, Artur j., ROMA-RODRIGUES, Catarina, PUTTREDDY, Rakesh, RISSANEN, Kari, BAPTISTA, Pedro viana, FERNANDES, Alexandra r., LIMA, João carlos, RODRÍGUEZ RAURELL, Laura. The important role of the nuclearity, rigidity, and solubility of phosphane ligands in the biological activity of gold(I) complexes. _Chemistry-A European Journal_. 2018. Vol. 24, núm. 55, pàgs. 14654-14667. [consulta: 23 de gener de 2026]. ISSN: 0947-6539. [Disponible a: https://hdl.handle.net/2445/152679]

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