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

• Published in: Inorganica Chimica Acta 2017-01, Vol.454, p.162-170
• Main Authors: Yano, Takakazu, Hishida, Shota, Nakai, Misaki, Nakabayashi, Yasuo
• Format: Article
• Language: English
• Subjects: Anticancer properties; Cancer therapies; Cytotoxicity; Deoxyribonucleic acid; DNA; Heterodinuclear Ru(II)–Pt(II) complexes; Lipophilicity; Photochemotherapeutic agents; Photocleavage; Photodynamic therapy; Plasmids; Platinum; Reactive oxygen species; Ruthenium; Ruthenium compounds; Singlet oxygen; Toxicity
• ISSN: 0020-1693; 1873-3255
• DOI: 10.1016/j.ica.2016.04.011

The heterodinuclear Ru(II)–Pt(II) complexes in this study were essentially nontoxic in the dark. On the other hand, the cytotoxicity of these complexes in the light were similar to cisplatin. [Display omitted] •Anticancer activity of heterodinuclear Ru(II)–Pt(II) complexes has been investigated.•All the complexes were cleavage inactive in the dark.•The photoinduced DNA cleavages were observed for these complexes.•The cytotoxicity of these complexes in the light may be due to the lipophilicity. The purpose of the present study was to investigate the DNA-binding properties of mononuclear ruthenium(II) complex [Ru(tBu2bpy)2(dpp)]2+ and heterodinuclear ruthenium(II)–platinum(II) complexes [Ru(tBu2bpy)2(μ-dpp)PtX2]2+ (X=Cl (1), Br (2), I (3)) and [Ru(bpy)2(μ-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(tBu2bpy)2(dpp)]2+ proceeded via a singlet oxygen pathway, whereas complexes 1–3 proceeded via a photoredox pathway. [Ru(tBu2bpy)2(dpp)]2+, 2, and 3 in the light displayed favorable cytotoxicity, which were in all cases similar to cisplatin. 2 (IC50=9.1μM) which was less toxic than [Ru(tBu2bpy)2(dpp)]2+ (IC50=5.6μM) 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).