title: Novel cis- and trans-configured bis(oxime)platinum(II) complexes: synthesis, characterization, and cytotoxic activity.
abstract: Novel cis- and trans-configured bis(oxime)platinum(II) complexes have been synthesized and characterized by elemental analyses, IR, electrospray ionization mass spectrometry, multinuclear ((1)H, (13)C, and (195)Pt) NMR spectroscopy, and, in five cases, by X-ray diffraction. Their cytotoxicity was studied in the cisplatin-sensitive CH1 cell line as well as in inherently cisplatin-resistant SW480 cancer cells. Remarkably, every single dihalidobis(oxime)platinum(II) complex (with either a cis or trans configuration) shows a comparable cytotoxic potency in both cell lines, indicating a capacity of overcoming cisplatin resistance. Particularly strong cytotoxicities were observed in the case of trans-[PtCl(2)(R(2)C=NOH)(2)] (R = Me, n-Pr, i-Pr) with IC(50) values in the high nanomolar concentration range in both CH1 and SW480 cancer cells. These complexes are as potent as cisplatin in CH1 cells and up to 20 times more potent than cisplatin in SW480 cells. In comparison to transplatin, the novel compounds are up to 90 (CH1) and 120 times (SW480) more cytotoxic. The previously reported observation that the trans geometry yields a more active complex in the case of [PtCl(2)(Me(2)C=NOH)(2)] could be confirmed for at least two structural analogues.
authors.affiliation: Institute of Inorganic Chemistry, University of Vienna, Währinger Strasse 42, A-1090 Vienna, Austria.
authors.forename: Yulia Yu
authors.initials: YY
authors.lastname: Scaffidi-Domianello
authors.forename: Kristof
authors.initials: K
authors.lastname: Meelich
authors.forename: Michael A
authors.initials: MA
authors.lastname: Jakupec
authors.forename: Vladimir B
authors.initials: VB
authors.lastname: Arion
authors.forename: Vadim Yu
authors.initials: VY
authors.lastname: Kukushkin
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*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds