title: Synthesis, characterization and in vitro antitumour activity of a series of novel platinum(II) complexes bearing Schiff base ligands.
abstract: A series was neutral platinum(II) complexes bearing OCH(3)- or F-substituted 3,4-bis(4-fluorophenyl)-1,6-bis(2-hydroxyphenyl)-2,5-diazahexa-1,5-dienes (diarylsalenes) were synthesized and tested for in vitro antitumour activity. The growth inhibitory effects depended on the configuration and the substitution pattern of the salicylidene moiety. The lead compound [meso-3,4-bis(4-fluorophenyl)-1,6-bis(2-hydroxyphenyl)-2,5-diazahexa-1,5-diene]platinum(II) (1-Pt) reduced the cell growth of MCF-7 (IC(50) = 7.6 μM) and MDA-MB 231 cells (IC(50) = 10.0 μM), but was inactive against HT-29 cells at the used concentration range (IC(50) > 20 μM). The change of the configuration (meso → d,l) at the 1,2-diimino-1,2-diarylethane bridge and methoxy substitution led to completely inactive compounds, while fluorine substituents increased the antiproliferative effects depending on their position (3-F < 5-F < 4-F < 6-F). Complex 10-Pt (6-F: IC(50)(MCF-7) = 1.5 μM, IC(50)(MDA-MB 231) = 1.3 μM, IC(50) (HT-29) = 2.6 μM) was as active as cisplatin (IC(50)(MCF-7) = 1.6 μM, IC(50)(MDA-MB 231) = 1.5 μM, IC(50)(HT-29) = 4.1 μM).
authors.affiliation: Institute of Pharmacy, Freie Universität Berlin, Königin-Luise-Str 2+4, 14195 Berlin, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Proetto
authors.forename: Wukun
authors.initials: W
authors.lastname: Liu
authors.forename: Adelheid
authors.initials: A
authors.lastname: Hagenbach
authors.forename: Ulrich
authors.initials: U
authors.lastname: Abram
authors.forename: Ronald
authors.initials: R
authors.lastname: Gust
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D006801:Humans; D020128:Inhibitory Concentration 50; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D009944:Organoplatinum Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D012545:Schiff Bases / Q000737:chemistry
chemical_list: D008024:Ligands; D009944:Organoplatinum Compounds; D012545:Schiff Bases