| Autor: |
Canil G; Department of Chemistry and Industrial Chemistry, University of Pisa, Via G. Moruzzi 13, 56124 Pisa, Italy. chiara.gabbiani@unipi.it., Braccini S; Department of Chemistry and Industrial Chemistry, University of Pisa, Via G. Moruzzi 13, 56124 Pisa, Italy. chiara.gabbiani@unipi.it., Marzo T; Department of Pharmacy, University of Pisa, Via Bonanno Pisano 6, 56126, Pisa, Italy. tiziano.marzo@unipi.it., Marchetti L; Department of Chemistry and Industrial Chemistry, University of Pisa, Via G. Moruzzi 13, 56124 Pisa, Italy. chiara.gabbiani@unipi.it., Pratesi A; MetMed Lab, Department of Chemistry 'U. Schiff', University of Florence, Via della Lastruccia 3, 50019 Sesto Fiorentino, Italy., Biver T; Department of Chemistry and Industrial Chemistry, University of Pisa, Via G. Moruzzi 13, 56124 Pisa, Italy. chiara.gabbiani@unipi.it and Department of Pharmacy, University of Pisa, Via Bonanno Pisano 6, 56126, Pisa, Italy. tiziano.marzo@unipi.it., Funaioli T; Department of Chemistry and Industrial Chemistry, University of Pisa, Via G. Moruzzi 13, 56124 Pisa, Italy. chiara.gabbiani@unipi.it., Chiellini F; Department of Chemistry and Industrial Chemistry, University of Pisa, Via G. Moruzzi 13, 56124 Pisa, Italy. chiara.gabbiani@unipi.it., Hoeschele JD; Department of Chemistry, Mark Jefferson Science Complex, Eastern Michigan University, Ypsilanti, Michigan 48197, USA., Gabbiani C; Department of Chemistry and Industrial Chemistry, University of Pisa, Via G. Moruzzi 13, 56124 Pisa, Italy. chiara.gabbiani@unipi.it. |
| Abstrakt: |
The use of Pt(iv) complexes as potential anticancer drugs is attractive, because they have higher stability and less side effects than Pt(ii) compounds. Moreover, some Pt(iv) complexes can also be activated with light, opening an avenue to photochemotherapy. Our purpose is to widen the library of photoactivatable Pt(iv)-based prodrugs and here we report on the oxidation of the Pt(ii) compound [PtCl(4'-phenyl-2,2':6',2''-terpyridine)][CF 3 SO 3 ] (1) with PhICl 2 or H 2 O 2 . The synthetic procedure avoids the formation of multiple species: the treatment with PhICl 2 produces the Pt(iv) complex with axial chlorides, [PtCl 3 (4'-phenyl-2,2':6',2''-terpyridine)][CF 3 SO 3 ] (2), while H 2 O 2 oxidation and post-synthesis carboxylation produce [Pt(OCOCH 3 ) 2 Cl(4'-phenyl-2,2':6',2''-terpyridine)][CF 3 SO 3 ] (3), bearing acetates in the axial positions. 2 and 3 are stable in physiological-like buffers and in DMSO in the dark, but undergo photoreduction to 1 upon irradiation at 365 nm. Their stability toward reduction is a fundamental parameter to consider: cyclic voltammetry experiments show that the 2 electron reduction Pt(iv) → Pt(ii) occurs at a more negative potential for 3, because of the greater stabilization provided by the acetate axial groups; noteworthily, 3 is stable for hours also in the presence of mM concentration of glutathione. The cytotoxicity of 2 and 3 toward A2780 and A2780cis cell lines reveals that 3 is the least toxic in the dark, but is able to produce cytotoxic effects far higher than cisplatin when irradiated. To shed light on the mechanistic aspects, the interaction with protein and DNA models has been explored through high-resolution mass spectrometry revealing that 2 and 3 behave as prodrugs, but are able to bind to biological targets only after irradiation. |
