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Synthesis, Characterization, and In Vitro Antitumor Activity of New Amidineplatinum(II) Complexes Obtained by Addition of Ammonia to Coordinated Acetonitrile

✍ Scribed by Francesco P. Intini; Raffaella Z. Pellicani; Angela Boccarelli; Rossella Sasanelli; Mauro Coluccia; Giovanni Natile


Publisher
John Wiley and Sons
Year
2008
Tongue
English
Weight
215 KB
Volume
2008
Category
Article
ISSN
1434-1948

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✦ Synopsis


Abstract

New cis‐ and __tran__s‐dichloridoplatinum(II) complexes, which contain two amidine ligands or one amidine and one ammine ligand, cis‐ and __tran__s‐[PtCl~2~{(Z)‐HN=C(NH~2~)CH~3~}~2~] (1) and cis‐ and trans‐[PtCl~2~(NH~3~){(Z)‐HN=C(NH~2~)CH~3~}] (2), have been prepared from the corresponding nitrile complexes by amminolysis in thf solution. All synthesized compounds were characterized by elemental analysis, ESI‐MS, and IR and NMR spectroscopy. Amidines are isosters of iminoethers and ketimines. The trans isomers of the platinum complexes of the latter are endowed with an unexpectedly high antitumor activity. An important feature of complexes 1 and 2, as compared to iminoethers, is the exclusive preference for the Z configuration of the amidine ligand(s). The tumor cell growth inhibitory potency of the amidine compounds was tested towards a pair of human ovarian tumor cell lines A2780 (cancer cells sensitive to cisplatin) and A2780cisR (cancer cells with acquired resistance to cisplatin), and compared to that of cisplatin. From the obtained results it appears that the resistance factor is lower for cis‐amidine complexes as compared to cisplatin, and for trans compounds it is lower as compared to cis compounds.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)