Ruthenium arene complexes with triphenylphosphane ligands: cytotoxicity towards pancreatic cancer cells, interaction with model proteins, and effect of ethacrynic acid substitution

被引:46
作者
Biancalana, Lorenzo [1 ]
Pratesi, Alessandro [2 ]
Chiellini, Federica [1 ]
Zacchini, Stefano [3 ]
Funaioli, Tiziana [1 ]
Gabbiani, Chiara [1 ]
Marchetti, Fabio [1 ]
机构
[1] Univ Pisa, Dipartimento Chim & Chim Ind, Via G Moruzzi 13, I-56124 Pisa, Italy
[2] Univ Firenze, MetMed, Dipartimento Chim Ugo Schiff, Via Lastruccia 3, I-50019 Sesto Fiorentino, Italy
[3] Univ Bologna, Dipartimento Chim Ind Toso Montanari, Viale Risorgimento 4, I-40136 Bologna, Italy
关键词
ORGANOMETALLIC RUTHENIUM(II)-ARENE COMPLEX; HALF-SANDWICH RUTHENIUM(II); ANTIPROLIFERATIVE ACTIVITY; ANTICANCER COMPLEXES; CONDUCTIVITY MEASUREMENTS; MASS-SPECTROMETRY; TRANSFERASE P1-1; OSMIUM COMPLEXES; METAL-COMPLEXES; CYTOCHROME-C;
D O I
10.1039/c7nj02300f
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
The ruthenium-arene complexes [(eta(6)-p-cymene)RuCl2(kP-PPh2(4-C6H4CO2H))], 1, [(eta(6)-p-cymene)RuCl(kappa P-2, O-PPh2( 2-C6H4CO2))], 2, [(eta(6)-p-cymene)RuCl2(kP-PPh2(2-C6H4OCO-EA))], 3, and [(eta(6)-p-cymene)RuCl2(kP-PPh2(4C(6)H(4)CO(2)CH(2)CH(2)OCO-EA))], 4 (EA-CO2H = ethacrynic acid), were synthesized in good to high yields and characterized by analytical techniques, IR, UV-Vis and multinuclear NMR spectroscopy, and single crystal X-ray diffraction in the cases of 1 and 2. The unstable compounds [(eta(6)-arene)RuCl2(kP-PPh2(2C(6)H(4)CO(2)CH(2)CH(2)OCO-EA))] (arene = p-cymene, 5a; arene = C6H6, 5b) were obtained and identified in solution by NMR. Electrochemical and spectro-electrochemical experiments were performed in order to assess the redox behaviour of 1-4 in CH2Cl2. The in vitro cytotoxicity of 1-4 was determined on the human pancreatic cancer cell line BxPC3 and the mouse embryo fibroblast Balb/3T3 Clone A31 cell line, the latter acting as a model for normal cells. Furthermore, the interaction of 1, 3 and 4 with two model proteins was investigated by high resolution ESI-MS.
引用
收藏
页码:14574 / 14588
页数:15
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