Diastereomerically pure platinum(II) complexes as antitumoral agents.: The influence of the mode of binding {(N), (N,O)− or (C,N)}− of (1S,2R)[(η5-C5H5)Fe{(η5-C5H4)CHNCH(Me)CH(OH)C6H5}] and the arrangement of the auxiliary ligands

The study of the reactivity of (1S,2R) [(η5-C5H5)Fe{[(η5-C5H4) CHNCH(Me)CH(OH)C6H5}] (1a) with cis-[PtCl2(DMSO)2] under different experimental conditions has allowed to isolate and characterize three pairs of isomeric and diastereomerically pure platinum(II) complexes. Two of the pairs are the trans- and cis- isomers of (1S,2R)[Pt{(η5-C5H5)Fe[(η5-C5H4)CHNCH(Me)CH(OH)C6H5]}Cl2(DMSO)] [trans-(2a) and cis-(3a), respectively], and of (1S,2R) [Pt{(κ2-N,O)(η5-C5H5)Fe[(η5-C5H4)CHNCH(Me)CH(O)C6H5]}Cl(DMSO)], {trans-(Cl, N) in (4a)} or a cis-(Cl, N) {in (5a)}; while the third one is formed by platinacycles: [Pt{(κ2-C,N[(η5-C5H3)]CHN-CH(Me)CH(OH)C6H5]Fe(η5-C5H5)}Cl(DMSO)] with different planar chirality [Sp (in 6a) or Rp (in 7a)]. The crystal structures of compounds 2a, 3a, 5a and 6a are also reported. The cytotoxic assessment of 1a–7a on lung (A549), breast (MDA-MB-231) and colon (HCT-116) cancer cell lines is also reported and reveals that the potency of the complexes is strongly dependent on the mode of binding of the iminoalcohol {(N) in 2a and 3a, (N,O)− in 4a and 5a or (C,N)− in 6a and 7a}, the relative arrangement of the monodentate ligands (in 2a–5a), and the planar chirality of the 1,2-ferrocenylunit in (6a and 7a). Among the new products (2a–7a), compounds 4a and 5a exhibit the highest potency with IC50 values smaller than cisplatin in the three cancer cell lines assayed. Electrophoretic DNA migration studies in the presence of 2a–7a have been performed in order to get further insights into their mechanism of action. A comparative study of the solution behaviour of all the complexes in DMSO-d6 or in DMSO-d6:D2O (1:1) mixtures at 298 K is also reported.

Graphical abstractSix novel platinum(II) complexes containing (1S,2R)[(η5-C5H5)Fe{[(η5-C5H4)CHNCH(Me)CH(OH)C6H5}] (1a) as an (N), (N,O)− or (C,N)− ligand are reported together with comparative studies of their antitumoral activity on lung (A549), breast (MDA MB231) and colon (HCT-116) cancer cell lines and their effect on electrophoretic DNA migration.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Six diastereomerically pure platinum(II) complexes as cytotoxic agents. ► Platinum(II) complexes with higher potency than cisplatin. ► Relationship between the mode of binding of the ligand and antitumoral activity. ► Platinacycles are more active than cis- or trans-[Pt(N-donor)Cl2(DMSO)] complexes. ► Highly potent [Pt(N, O)Cl(DMSO)] compounds (IC50 = 1.4 μM) in two cancer cell lines.