title: 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.
abstract: The study of the reactivity of (1S,2R) [(η(5)-C(5)H(5))Fe{[(η(5)-C(5)H(4)) CHNCH(Me)CH(OH)C(6)H(5)}] (1a) with cis-[PtCl(2)(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{(η(5)-C(5)H(5))Fe[(η(5)-C(5)H(4))CHNCH(Me)CH(OH)C(6)H(5)]}Cl(2)(DMSO)] [trans-(2a) and cis-(3a), respectively], and of (1S,2R) [Pt{(κ(2)-N,O)(η(5)-C(5)H(5))Fe[(η(5)-C(5)H(4))CHNCH(Me)CH(O)C(6)H(5)]}Cl(DMSO)], {trans-(Cl, N) in (4a)} or a cis-(Cl, N) {in (5a)}; while the third one is formed by platinacycles: [Pt{(κ(2)-C,N[(η(5)-C(5)H(3))]CHN-CH(Me)CH(OH)C(6)H(5)]Fe(η(5)-C(5)H(5))}Cl(DMSO)] with different planar chirality [S(p) (in 6a) or R(p) (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 IC(50) 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-d(6) or in DMSO-d(6):D(2)O (1:1) mixtures at 298 K is also reported.
authors.affiliation: Departament de Química Inorgànica, Facultat de Química, Universitat de Barcelona, Martí i Franquès 1-11, E-08028-Barcelona, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Talancón
authors.forename: Concepción
authors.initials: C
authors.lastname: López
authors.forename: Mercè
authors.initials: M
authors.lastname: Font-Bardía
authors.forename: Teresa
authors.initials: T
authors.lastname: Calvet
authors.forename: Josefina
authors.initials: J
authors.lastname: Quirante
authors.forename: Carme
authors.initials: C
authors.lastname: Calvis
authors.forename: Ramon
authors.initials: R
authors.lastname: Messeguer
authors.forename: Roldán
authors.initials: R
authors.lastname: Cortés
authors.forename: Marta
authors.initials: M
authors.lastname: Cascante
authors.forename: Laura
authors.initials: L
authors.lastname: Baldomà
authors.forename: Josefa
authors.initials: J
authors.lastname: Badia
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D053938:DNA Fragmentation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D008968:Molecular Conformation; D010957:Plasmids / Q000737:chemistry; D010984:Platinum; D013237:Stereoisomerism
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D010984:Platinum; D002945:Cisplatin