Two New Co(II) and Ni(II) Complexes with 3-(2-Pyridyl)pyrazole-Based Ligand : Synthesis, Crystal Structures, and Bioactivities

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Two new Co(II) and Ni(II) complexes exhibiting DNA cytotoxic activities with 3-(2-pyridyl)pyrazole-based ligand, [Co(L)_3](ClO_4)_2 (1) and [Ni(L)_3](ClO_4)_2 (2) (L= 1-[3-(2-pyridyl)-pyrazol-1-ylmethyl]-naphthalene) were synthesized and structurally characterized. Both 1 and 2 crystallized in the monoclinic system, space group P2(1)/c, for 1, a=12.8324(8), b=12.1205(8), c=33.27(2)Å, β=93.92(3)° and Z=4; for 2, a=12.8764(3), b=12.1015(3), c=33.2415(9)Å, β=93.998(1)° and Z=4. Among them, the Co(II) and Ni(II) ions were all coordinated by six N donors from three distinct L ligands. In addition, the cytotoxic activities of 1, 2 and L in vitro were evaluated against three different cancer cell lines HL-60 (human leukemia), BGC-823 (stomach cancer) and MDA-MB-435 (mammary cancer), respectively. The results showed that 1 exhibited significantly high cytotoxic activities against HL-60 and moderate activities against BGC-823 and MDA-MB-435. In order to further investigate the relationships between structures and DNA-binding behaviors of these complexes, the interactions of 1, 2 and L with calf thymus DNA (CT-DNA) were then subjected to thermal denaturation, viscosity measurements and spectrophotometric methods. The results indicated that 1 and 2 intercalated with DNA via L ligand. The intrinsic binding constants of 1, 2 and L with DNA were 1.6×10^4, 5.6×10^3 and 2.76×10^3M^<-1>, respectively.
公益社団法人日本薬学会の論文
2007-07-01