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- Title
Bis-intercalative dinuclear platinum(II) 6-phenyl-2,2'-bipyridine complexes exhibit enhanced DNA affinity but similar cytotoxicity compared to the mononuclear unit.
- Authors
Hing-Leung Chan; Dik-Lung Ma; Mengsu Yang; Chi-Ming Che
- Abstract
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.
- Subjects
PLATINUM compounds; CLATHRATE compounds; ABSORPTION; DNA
- Publication
Journal of Biological Inorganic Chemistry (JBIC), 2003, Vol 8, Issue 7, p761
- ISSN
0949-8257
- Publication type
Article
- DOI
10.1007/s00775-003-0477-0