Bis-intercalative dinuclear platinum(II) 6-phenyl-2,2′-bipyridine complexes exhibit enhanced DNA affinity but similar cytotoxicity compared to the mononuclear unit

被引:39
|
作者
Chan, HL
Ma, DL
Yang, MS
Che, CM
机构
[1] City Univ Hong Kong, Dept Biol & Chem, Kowloon, Hong Kong, Peoples R China
[2] Univ Hong Kong, Dept Chem, Hong Kong, Hong Kong, Peoples R China
[3] Univ Hong Kong, Open Lab Chem Biol, Inst Mol Technol Drug Discovery & Synth, Hong Kong, Hong Kong, Peoples R China
来源
关键词
bisintercalation; cytotoxicity; DNA binding; platinum;
D O I
10.1007/s00775-003-0477-0
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The interactions between a series of platinum complexes, including (pyridyl)(6-phenyl-2,2'-bipyridine)platinum(II) hexafluorophosphate (1), three dinuclear bis[(6-phenyl-2,2'-bipyridine)platinum(II)] complexes (2-4), and (4-aminopyridine)(4,6-diphenyl-2,2'-bipyridine)platinum(II) perchlorate (5) with DNA have been investigated. All Pt(II) complexes, except 5, were demonstrated to be DNA intercalators, based on viscosity measurements. Absorption and fluorescence titration results indicated that the addition of a phenyl ring to the 6-phenyl-2,2'-bipyridine ligand dramatically reduced the DNA binding of the Pt(II) complex 5. The dinuclear complexes 2-4 exhibited multiple binding modes of mono/bisintercalation and groove binding, as revealed by viscosity and fluorescence titration measurements. While complexes 2-4 bound to DNA with significantly enhanced affinities as compared to 1, compounds 1 and 2-4 showed similar IC50 values against a panel of cancer cell lines. In addition, these complexes showed similar cellular uptakes. The results indicated that the cytotoxicity of these (6-phenyl-2,2'-bipyridine)platinum compounds may not be mediated through DNA binding but may involve interacting mechanisms with cellular components other than DNA.
引用
收藏
页码:761 / 769
页数:9
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