Department of biophysics Palacky University


HomeResearch topicsCollaborationPublications

Preparation and in vitro evaluation of bis(5-phenyltetrazolato) Pt(II) and Pt(IV) analogues of transplatin for antitumor activity.

Autor: Perfahl S., Bodtke A., Pracharova J., Kasparkova J., Brabec V., Cuadrado J., Stürup S., Schulzke C., Bednarski P.J.Published: Inorganica Chimica Acta 456, 86-94Year: 2017

To evaluate the 5-substituted tetrazolate (5R-tetrazolate) ligand for the development of novel antitumor active Pt(II) and Pt(IV) diamines, eight analogues of transplatin bearing 5-phenyltetrazolato and 5-(phenol)tetrazolato ligands were prepared by reacting transplatin with the 5-substituted tetrazolate in DMF in the presence of trimethylamine. Coordination to platinum was through the N2 position of the tetrazolato ligand, as evidenced by a X-ray crystal structure of trans-diamminobis[5-(phenyl-4-ol)tetrazolato-kappaN2]platinum(II). Attempts to synthesize the corresponding cis-coordinated analogues from cisplatin were unsuccessful due to isomerization to the more stable trans isomers. Hydrogen peroxide was used to oxidize trans-diamminobis(5-phenyltetrazolato) and trans-diamminobis(5-phenoltetrazolato)platinum(II) complexes to the trans-dihydroxo-Pt(IV) analogues; the hydroxo ligands were then further acylated. The binding of Pt to calf thymus DNA for trans,trans,trans-diamminodihydroxidobis(5-phenyltetrazolato-kN2)platinum(IV) was dependent on the presence of ascorbate; however, the Pt(II) analogue trans-diamminobis(5-phenyltetrazolato-kappaN2)platinum(II) itself bond only very weakly to DNA, indicating that this is not the product of the ascorbate induced reduction of the Pt(IV) complex. Evaluation of the antiproliferative activity on six human cancer cells in vitro showed the Pt(IV) complexes to be more potent than the Pt(II) analogues but all complexes were still much less active than cisplatin. No cross resistance to cisplatin was observed in the A2870 ovarian cancer cell line.


Department of Biophysics

Faculty of Science

Palacký University in Olomouc, Czech Republic

© 2011 Department of Biophysics
Created: Webdesign Olomouc | Artprodesign.com