TY - JOUR
T1 - The Important Role of the Nuclearity, Rigidity, and Solubility of Phosphane Ligands in the Biological Activity of Gold(I) Complexes
AU - Svahn, Noora
AU - Moro, Artur J.
AU - Roma-Rodrigues, Catarina
AU - Puttreddy, Rakesh
AU - Rissanen, Kari
AU - Baptista, Pedro V.
AU - Fernandes, Alexandra R.
AU - Lima, João Carlos
AU - Rodríguez, Laura
N1 - Sem PDF conforme despacho.
info:eu-repo/grantAgreement/FCT/5876/147218/PT#
info:eu-repo/grantAgreement/FCT/5876/147258/PT#
The authors are grateful to the Ministry of Economy, Industry and Competitiveness of Spain (AEI/FEDER, UE Project CTQ2016-76120-P). This work was also supported by the Associated Laboratory for Sustainable Chemistry, Clean Processes and Technologies, LAQV, which is financed by national funds from FCT/MEC (UID/QUI/50006/2013) and co-financed by the ERDF under the PT2020 Partnership Agreement (POCI-01-0145-FEDER-007265) and by the Unidade de Cithornncias Biomoleculares Aplicadas-UCIBIO, which is financed by national funds from FCT/MEC (UID/Multi/04378/2013) and co-financed by the ERDF under the PT2020 Partnership Agreement (POCI-01-0145-FEDER-007728). COST Action CM1402 is also acknowledged. N.S. is also indebted to the Erasmus exchange mobility program. We also would like to thank Ms. Andrea Pinto and Mr. Oussama Kheireedine Nehar for the help in some of the syntheses performed. The University of Jyvaskyla (K.R.) and The Academy of Finland (R.P., grant no. 298817) are kindly acknowledged for financial support.
PY - 2018/10/1
Y1 - 2018/10/1
N2 - 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.
AB - 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.
KW - antitumor agents
KW - apoptosis
KW - biological activity
KW - gold
KW - X-ray diffraction
UR - http://www.scopus.com/inward/record.url?scp=85054065949&partnerID=8YFLogxK
U2 - 10.1002/chem.201802547
DO - 10.1002/chem.201802547
M3 - Article
C2 - 30063270
AN - SCOPUS:85054065949
SN - 0947-6539
VL - 24
SP - 14654
EP - 14667
JO - Chemistry - A European Journal
JF - Chemistry - A European Journal
IS - 55
ER -
