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

Chemistry - A European Journal - Tập 24 Số 55 - Trang 14654-14667 - 2018
Noora Svahn1, Artur J. Moro2, Catarina Roma‐Rodrigues3, Rakesh Puttreddy4, Kari Rissanen4, Pedro V. Baptista3, Alexandra R. Fernandes3, João Carlos Lima2, Laura Rodrı́guez1,5
1Departament de Química Inorgànica i Orgànica, Secció de Química Inorgànica Universitat de Barcelona Martí i Franquès 1–11 08028 Barcelona Spain
2LAQV-REQUIMTE, Departamento de Química, CQFB, Universidade Nova de Lisboa, Monte de Caparica, Portugal
3UCIBIO, Departamento de Ciências da Vida, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, Campus de Caparica, 2829-516 Caparica, Portugal
4Department of Chemistry, Nanoscience Center University of Jyvaskyla P.O. Box 35 40014 Jyväskylä Finland
5Institut de Nanociència i Nanotecnologia (IN2UB), Universitat de Barcelona, 08028 Barcelona, Spain

Tóm tắt

AbstractA 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.

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Chemistry - A European Journal

Tập 24 Số 55

14654-14667

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