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- Title
A dinuclear monofunctional platinum(II) complex with an aromatic linker shows low reactivity towards glutathione but high DNA binding ability and antitumor activity.
- Authors
Damin Fan; Xiaoliang Yang; Xiaoyong Wang; Shouchun Zhang; Jiafei Mao; Jian Ding; Liping Lin; Zijian Guo
- Abstract
Multinuclear Pt(II) complexes represent a novel class of antitumor agents. In this work, a dinuclear monofunctional Pt(II) complex {[ cis-Pt(NH3)2Cl]2(4,4′-methylenedianiline)}(NO3)2 ( 1) was synthesized and characterized by 1H NMR, electrospray mass spectrometry, and elemental analysis. The 2D [1H,15N] heteronuclear single quantum coherence NMR spectra of 15N-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.
- Subjects
ANTINEOPLASTIC agents; CISPLATIN; DRUG side effects; GLUTATHIONE; HYDROLYSIS; MOUSE leukemia
- Publication
Journal of Biological Inorganic Chemistry (JBIC), 2007, Vol 12, Issue 5, p655
- ISSN
0949-8257
- Publication type
Article
- DOI
10.1007/s00775-007-0214-1