title: A dinuclear monofunctional platinum(II) complex with an aromatic linker shows low reactivity towards glutathione but high DNA binding ability and antitumor activity.
abstract: Multinuclear Pt(II) complexes represent a novel class of antitumor agents. In this work, a dinuclear monofunctional Pt(II) complex {[cis-Pt(NH(3))(2)Cl](2)(4,4'-methylenedianiline)}(NO(3))(2) (1) was synthesized and characterized by (1)H NMR, electrospray mass spectrometry, and elemental analysis. The 2D [(1)H,(15)N] heteronuclear single quantum coherence NMR spectra of (15)N-labeled 1 revealed that the cationic core of this water-soluble complex hardly hydrolyzes in aqueous solution and reacts very slowly with glutathione. Hydrolysis appears not to be an essential step for the formation of Pt-guanosine-5'-monophosphate (5'-GMP) or Pt-DNA adducts because the complex can react readily with 5'-GMP and partially transform B-DNA into its Z form. Such properties are desired to achieve the goal of enhancing cytotoxicity and lowering side effects of Pt(II) complexes. In fact, complex 1 is highly cytotoxic against the murine leukemia (P-388) and the human non-small-cell lung cancer (A-549) cell lines, and it is more cytotoxic than cisplatin at most concentrations tested.
authors.affiliation: State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, People's Republic of China.
authors.forename: Damin
authors.initials: D
authors.lastname: Fan
authors.forename: Xiaoliang
authors.initials: X
authors.lastname: Yang
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Wang
authors.forename: Shouchun
authors.initials: S
authors.lastname: Zhang
authors.forename: Jiafei
authors.initials: J
authors.lastname: Mao
authors.forename: Jian
authors.initials: J
authors.lastname: Ding
authors.forename: Liping
authors.initials: L
authors.lastname: Lin
authors.forename: Zijian
authors.initials: Z
authors.lastname: Guo
mesh_terms: D000814:Aniline Compounds; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D045744:Cell Line, Tumor; D002942:Circular Dichroism; D004247:DNA / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism*; D006157:Guanosine Monophosphate / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D007202:Indicators and Reagents; D007941:Leukemia P388 / Q000188:drug therapy; D008175:Lung Neoplasms / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization; D001559:Benzhydryl Compounds
chemical_list: D000814:Aniline Compounds; D000970:Antineoplastic Agents; D004247:DNA; D005978:Glutathione; D006157:Guanosine Monophosphate; D007202:Indicators and Reagents; D009944:Organoplatinum Compounds; C009505:4,4'-diaminodiphenylmethane; D001559:Benzhydryl Compounds; C114062:BBR 3464