Anticancer activity of heterodinuclear ruthenium(II)-platinum(II) complexes as photochemotherapeutic agents

作者：Yano Takakazu; Hishida Shota; Nakai Misaki; Nakabayashi Yasuo^*

来源：Inorganica Chimica Acta, 2017, 454: 162-170.

DOI：10.1016/j.ica.2016.04.011

• Heterodinuclear Ru(II)-Pt(II) complexes
• Photochemotherapeutic agents
• Photocleavage
• Reactive oxygen species
• Cytotoxicity

The purpose of the present study was to investigate the DNA-binding properties of mononuclear ruthenium(II) complex [Ru((t)Bu(2)bPy)(2)(dpp)](2+) and heterodinuclear ruthenium(II)-platinum(II) complexes [Ru((t)Bu(2)bpy)(2)(mu-dpp)PtX2](2+) (X = Cl (1), Br (2), I (3)) and [Ru(bpy)(2)(mu-dpp)PtCl2](2+) (4). We presented the interaction study of the complexes with CT-DNA and the DNA photocleavage properties using pBR322 supercoiled plasmid DNA when irradiated with visible light and their cytotoxicity against HeLa cervical cancer cell line. All the complexes were cleavage inactive in the dark, while the photoinduced DNA cleavages were observed for these complexes. It appeared that the DNA photocleavage for [Ru((t)Bu(2)bpy)(2)(dpp)](2+) proceeded via a singlet oxygen pathway, whereas complexes 1-3 proceeded via a photoredox pathway. [Ru((t)Bu(2)bpy)(2)(dpp)](2+), 2, and 3 in the light displayed favorable cytotoxicity, which were in all cases similar to cisplatin. 2 (IC50 = 9.1 mu M) which was less toxic than [Ru((t)Bu(2)bpy)(2)(dpp)](2+) (IC50 = 5.6 mu M) produced the largest PI (>22), indicating a highly effective photocytotoxic agent. The order of cytotoxicity of 1-4 in the light may be due to the lipophilicity (2 > 3 > 1 >> 4).

• 出版日期2017-1-1