Chan Hing-Leung, Ma Dik-Lung, Yang Mengsu, Che Chi-Ming
Department of Biology and Chemistry, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong, China.
J Biol Inorg Chem. 2003 Sep;8(7):761-9. doi: 10.1007/s00775-003-0477-0. Epub 2003 Jul 22.
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 IC(50) 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.
已对一系列铂配合物与DNA的相互作用进行了研究，这些铂配合物包括（吡啶基）（6-苯基-2,2'-联吡啶）铂（II）六氟磷酸盐（1）、三种双核双[（6-苯基-2,2'-联吡啶）铂（II）]配合物（2 - 4）以及（4-氨基吡啶）（4,6-二苯基-2,2'-联吡啶）铂（II）高氯酸盐（5）。基于粘度测量，除5之外的所有Pt（II）配合物均被证明是DNA嵌入剂。吸收和荧光滴定结果表明，在6-苯基-2,2'-联吡啶配体上添加一个苯环会显著降低Pt（II）配合物5与DNA的结合。粘度和荧光滴定测量结果表明，双核配合物2 - 4表现出单/双嵌入和沟槽结合的多种结合模式。虽然与1相比，配合物2 - 4与DNA结合的亲和力显著增强，但化合物1和2 - 4对一组癌细胞系显示出相似的IC50值。此外，这些配合物表现出相似的细胞摄取情况。结果表明，这些（6-苯基-2,2'-联吡啶）铂化合物的细胞毒性可能不是通过与DNA结合介导的，而是可能涉及与DNA以外的细胞成分的相互作用机制。
