title: Cytotoxicity and antitumor activity of bis(platinum) complexes. A novel class of platinum complexes active in cell lines resistant to both cisplatin and 1,2-diaminocyclohexane complexes.
abstract: The in vitro cytotoxicity and in vivo antitumor activity of bis(platinum) complexes of general formula [(PtX2-(L))2H2N(CH2)nNH2] (L = NH3, X = Cl or X2 = malonato or where L = py, X = Cl) is reported. Chloride complexes [(PtCl2(NH3]2H2N(CH2)nNH2] may exist as three possible isomers: those containing both coordination units in the cis configuration (2,2/c,c), both coordination units in the trans configuration (2,2/t,t), and the mixed cis,trans species (2,2/c,t), whose synthesis is reported here. The preparation of further complexes with sterically hindered diamine backbones, such as 2,5-dimethyl-2,5-hexanediamine, is exemplified. The biological activity of all complexes were compared. The 2,2/c,c complexes are particularly active in tissue culture in cells resistant both to cisplatin and its 1,2-diaminocyclohexane (dach) analogue. The inhibition of DNA synthesis in L1210/0 cells by the 2,2/c,c complexes is equivalent to that of cisplatin. The presence of at least one cis-[Pt(amine)2] unit appears necessary for activity in cell lines sensitive to cisplatin.
authors.affiliation: Department of Chemistry, University of Vermont, Burlington 05405.
authors.forename: N
authors.initials: N
authors.lastname: Farrell
authors.forename: Y
authors.initials: Y
authors.lastname: Qu
authors.forename: M P
authors.initials: MP
authors.lastname: Hacker
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin; D003514:Cyclohexylamines; D004247:DNA / Q000096:biosynthesis; D004351:Drug Resistance; D007939:Leukemia L1210 / Q000188:drug therapy / Q000378:metabolism; D007941:Leukemia P388 / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D015394:Molecular Structure; D009944:Organoplatinum Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D003514:Cyclohexylamines; D009944:Organoplatinum Compounds; D004247:DNA; C030435:1,2-cyclohexanediamine; D002945:Cisplatin