Solution behaviour and biological activity of bisamidine complexes of platinum(II)

C. Marzano, S. Mazzega Sbovata, F. Bettio, R. A. Michelin, R. Seraglia, T. Kiss, A. Venzo, R. Bertani

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Abstract

A series of platinum(II) amidine complexes were previously prepared with the aim of obtaining a new class of platinum-based antitumour drugs. This series includes compounds of the type cis - [PtCl2{Z-HN=C(NHMe)Me} 2] and trans-[PtCl2{Z-HN=C(NHMe)Me}2] (1, 2), cis-[PtCl2{E-HN=C(NMe2)Me}2] and trans-[PtCl2{E-HN=C(NMe2)Me}2] (3, 4), cis-[PtCl2{Z-HN=C(NHMe)Ph}2] and trans-[PtCl 2{Z-HN=C(NHMe)Ph}2] (5, 6), and cis-[PtCl 2{HN=C(NMe2)Ph}2] and trans-[PtCl 2{HN=C(NMe2)Ph}2] (7, 8). The reactions with dimethyl sulfoxide were studied for complexes 5-8; the formation of cationic species containing coordinated dimethyl sulfoxide was demonstrated by NMR experiments and electrospray ionization mass spectrometry. In this work, the amidine platinum(II) complexes were tested for their in vitro cytotoxicity on a panel of various human cancer cell lines. The results indicate that the benzamidine complex 8 was the most effective derivative also circumventing acquired cisplatin resistance as demonstrated by chemosensitivity tests performed on cisplatin-sensitive and cisplatin-resistant cell lines. The studies concerning the cellular DNA damage on both parental chemosensitive and resistant sublines suggest for the new trans-amidine complex a different mechanism of action compared with that exhibited by cisplatin.

Original languageEnglish
Pages (from-to)477-493
Number of pages17
JournalJournal of Biological Inorganic Chemistry
Volume12
Issue number4
DOIs
Publication statusPublished - May 2007

Fingerprint

Amidines
Bioactivity
Platinum
Cisplatin
Dimethyl Sulfoxide
Cells
Cell Line
Electrospray ionization
Electrospray Ionization Mass Spectrometry
Cytotoxicity
Antineoplastic Agents
DNA Damage
Mass spectrometry
Nuclear magnetic resonance
Derivatives
bisamidine
DNA
Neoplasms
Experiments

Keywords

  • Cisplatin
  • Cytotoxicity
  • Drug resistance
  • Platinum amidine complexes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry

Cite this

Marzano, C., Sbovata, S. M., Bettio, F., Michelin, R. A., Seraglia, R., Kiss, T., ... Bertani, R. (2007). Solution behaviour and biological activity of bisamidine complexes of platinum(II). Journal of Biological Inorganic Chemistry, 12(4), 477-493. https://doi.org/10.1007/s00775-006-0202-x

Solution behaviour and biological activity of bisamidine complexes of platinum(II). / Marzano, C.; Sbovata, S. Mazzega; Bettio, F.; Michelin, R. A.; Seraglia, R.; Kiss, T.; Venzo, A.; Bertani, R.

In: Journal of Biological Inorganic Chemistry, Vol. 12, No. 4, 05.2007, p. 477-493.

Research output: Contribution to journalArticle

Marzano, C, Sbovata, SM, Bettio, F, Michelin, RA, Seraglia, R, Kiss, T, Venzo, A & Bertani, R 2007, 'Solution behaviour and biological activity of bisamidine complexes of platinum(II)', Journal of Biological Inorganic Chemistry, vol. 12, no. 4, pp. 477-493. https://doi.org/10.1007/s00775-006-0202-x
Marzano, C. ; Sbovata, S. Mazzega ; Bettio, F. ; Michelin, R. A. ; Seraglia, R. ; Kiss, T. ; Venzo, A. ; Bertani, R. / Solution behaviour and biological activity of bisamidine complexes of platinum(II). In: Journal of Biological Inorganic Chemistry. 2007 ; Vol. 12, No. 4. pp. 477-493.
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