Metals in medicine: metal-related diseases-Antitumor activity of heterodinuclear ruthenium(II)– platinum(II) complexes as photochemotherapeutic agents

摘要

Cisplatin (cis-[PtCl_2(NH_3)_2]) has been one of the leading anticancer drug for near 30 years. However, cisplatin has several drawbacks such as toxicity and drug resistance. Ru(II)–polypyridine complexes were proposed as potential antitumor substances with non-covalent interactions and available for photodynamic therapy (PDT). In this study, we have synthesized heterodinuclear Ru(II)–Pt(II) (1–6) and mononuclear Ru(II) (7 and 8) complexes, and evaluated DNA photocleavage ability. The interactions of these complexes with DNA have been investigated by spectroscopic (UV–Vis, fluorescence, ESR) and agarose gel electrophoretic methods. In addition, the cytotoxicity of 1–8 were also determined using the MTT assay in Hela cell lines. All the complexes can photocleave pBR322 DNA with visible light radiation (xenon lamp, 300 W) through both ?OH and ~1O_2 (1–6) and ~1O_2 (7, 8) generation mechanisms [1]. The DNA photocleavage ability of 1–6 is higher than that of 7 and 8. Furthermore, in the series of 1–6 DNA photocleavage ability of 1–3 (R = H) is higher than that of 4–6 (R = tert-Bu). 1 and 4 (X = Cl~-) can bind covalently to DNA through the dissociation of Cl- in low Cl~- concentration (0–15 mM). On the other hand, 2, 3, 5 and 6 interact with DNA by non-covalent mode. 1–6 exhibit higher cytotoxicity compared to 7 and 8. Moreover, 4–6 are found to be more cytotoxic than 1–3, that is, 4–6 may be expected to be applied to antitumor drugs that reduce the drawbacks and increase the effects.