Bis-intercalative dinuclear platinum(II) 6-phenyl-2,2'-bipyridine complexes exhibit enhanced DNA affinity but similar cytotoxicity compared to the mononuclear unit.
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.
Chan
Hing-Leung
HL
Department of Biology and Chemistry, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong, China.
Ma
Dik-Lung
DL
Yang
Mengsu
M
Che
Chi-Ming
CM
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007364:Intercalating Agents / Q000138:chemical synthesis / Q000494:pharmacology; D009690:Nucleic Acid Conformation / Q000187:drug effects; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D011725:Pyridines / Q000138:chemical synthesis / Q000494:pharmacology*; D013057:Spectrum Analysis; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D007364:Intercalating Agents; D009944:Organoplatinum Compounds; D011725:Pyridines; C478898:platinum(II) 6-phenyl-2,2'-bipyridine; D004247:DNA