title: Unsymmetric mono- and dinuclear platinum(IV) complexes featuring an ethylene glycol moiety: synthesis, characterization, and biological activity.
abstract: Eight novel mononuclear and two dinuclear platinum(IV) complexes were synthesized and characterized by elemental analysis, one- and two-dimensional NMR spectroscopy, mass spectrometry, and reversed-phase HPLC (log k(w)) and in one case by X-ray diffraction. Cytotoxicity of the compounds was studied in three human cancer cell lines (CH1, SW480, and A549) by means of the MTT assay, featuring IC(50) values to the low micromolar range. Furthermore a selected set of compounds was investigated in additional cancer cell lines (P31 and P31/cis, A2780 and A2780/cis, SW1573, 2R120, and 2R160) with regard to their resistance patterns, offering a distinctly different scheme compared to cisplatin. To gain further insights into the mode of action, drug uptake, DNA synthesis inhibition, cell cycle effects, and induction of apoptosis were determined for two characteristic substances.
authors.affiliation: Institute of Inorganic Chemistry, University of Vienna, Waehringer Strasse 42, A-1090 Vienna, Austria.
authors.forename: Verena
authors.initials: V
authors.lastname: Pichler
authors.forename: Petra
authors.initials: P
authors.lastname: Heffeter
authors.forename: Seied M
authors.initials: SM
authors.lastname: Valiahdi
authors.forename: Christian R
authors.initials: CR
authors.lastname: Kowol
authors.forename: Alexander
authors.initials: A
authors.lastname: Egger
authors.forename: Walter
authors.initials: W
authors.lastname: Berger
authors.forename: Michael A
authors.initials: MA
authors.lastname: Jakupec
authors.forename: Mathea Sophia
authors.initials: MS
authors.lastname: Galanski
authors.forename: Bernhard K
authors.initials: BK
authors.lastname: Keppler
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D017209:Apoptosis; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D056148:Chromatography, Reverse-Phase; D002945:Cisplatin / Q000494:pharmacology; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D018360:Crystallography, X-Ray; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D005026:Ethylene Glycols / Q000737:chemistry*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010984:Platinum; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D012995:Solubility; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D005026:Ethylene Glycols; D011355:Prodrugs; D010984:Platinum; D002945:Cisplatin