title: Antitumor and DNA-binding properties of a group of oligomeric complexes of Pt(II) and Pt(IV).
abstract: The antitumor and DNA-binding properties of a group of oligomeric platinum(II) and platinum(IV) complexes are described. The compounds, having the stoichiometry [cis-PtII(X)2(mu-OH)]2(NO3)2, where X is NH3, NH2CH2CH3, and NH2CH(CH3)2, were found to be inactive or only weakly active against L-1210 leukemia. In vitro studies involving PM2-DNA show that these compounds bind to and unwind closed circular DNA in a manner similar to cis-PtII-(NH3)2Cl2. The Pt(IV) complexes produced by hydrogen peroxide oxidation of the Pt(II) dimers are inactive as antitumor agents and are incapable of unwinding PM2-DNA. The cyclotrimer [cis-PtII(RR-DACH)(mu-OH)]3(NO3)3, where RR-DACH is (R,R)-1,2 diaminocyclohexane, exhibits potent antitumor activity against L-1210 leukemia and modest activities with B-16 and M5076 tumor lines. This compound platinates DNA, causing DNA unwinding and mobility shifts.
authors.affiliation: Department of Chemistry, Syracuse University, New York 13244-4100.
authors.forename: A
authors.initials: A
authors.lastname: Peritz
authors.forename: S
authors.initials: S
authors.lastname: al-Baker
authors.forename: J F
authors.initials: JF
authors.lastname: Vollano
authors.forename: J E
authors.initials: JE
authors.lastname: Schurig
authors.forename: W T
authors.initials: WT
authors.lastname: Bradner
authors.forename: J C
authors.initials: JC
authors.lastname: Dabrowiak
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000627:therapeutic use*; D004247:DNA / Q000378:metabolism*; D004270:DNA, Circular / Q000378:metabolism; D006861:Hydrogen Peroxide; D007939:Leukemia L1210 / Q000188:drug therapy; D046911:Macromolecular Substances; D051379:Mice; D009944:Organoplatinum Compounds / Q000378:metabolism / Q000627:therapeutic use*; D010084:Oxidation-Reduction; D011355:Prodrugs; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D004270:DNA, Circular; D046911:Macromolecular Substances; D009944:Organoplatinum Compounds; D011355:Prodrugs; D004247:DNA; D006861:Hydrogen Peroxide