Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, P. R. China.
Dalton Trans. 2019 May 15;48(19):6492-6500. doi: 10.1039/c9dt00441f.
Ru(ii) polypyridyl complexes which can undergo photo-induced ligand dissociation and DNA covalent binding are considered as potential photoactivated chemotherapeutic (PACT) agents. Herein four pyridine-2-sulfonate (py-SO3-) ligand based Ru(ii) complexes [Ru(N-N)2(py-SO3)]+ (1-4) were synthesized and studied. All the complexes can undergo fast py-SO3- ligand dissociation and DNA covalent binding upon visible light irradiation. However, only complex 4 exhibited high photo-induced anticancer activities towards a series of cancer cells, with half maximal inhibitory concentration (IC50) values in 100-300 nM regions and phototoxicity index (PI) values of about 100. In particular, complex 4 can also kill cisplatin resistant SKOV-3 and A549 cancer cells with IC50 values in 200-400 nM regions and PI values of about 50, which should be the first report of Ru(ii) based PACT agents that are also effective towards cisplatin resistant cancer cells. Complex 4 exhibited much higher cell uptake and nuclear accumulation levels, which may be the main reasons for its high anticancer activities. The in vivo anticancer experiments indicated that complex 4 can inhibit tumor growth significantly with fewer side effects. Our results may provide guidelines for developing novel photoactivatable Ru(ii) anticancer agents.
钌（II）金属配合物可以经历光诱导的配体解离和 DNA 共价结合，被认为是潜在的光激活化疗（PACT）药物。本文合成并研究了四种基于吡啶-2-磺酸盐（py-SO3-）配体的 Ru(ii) 配合物 [Ru(N-N)2(py-SO3)]+（1-4）。所有配合物在可见光照射下都能快速发生 py-SO3-配体解离和 DNA 共价结合。然而，只有配合物 4 对一系列癌细胞表现出高的光诱导抗癌活性，半数最大抑制浓度（IC50）值在 100-300 nM 范围内，光毒性指数（PI）值约为 100。特别是，配合物 4 还可以杀死顺铂耐药的 SKOV-3 和 A549 癌细胞，IC50 值在 200-400 nM 范围内，PI 值约为 50，这应该是首例报道对顺铂耐药癌细胞也有效的基于 Ru(ii)的 PACT 药物。配合物 4 表现出更高的细胞摄取和核积累水平，这可能是其高抗癌活性的主要原因。体内抗癌实验表明，配合物 4 能显著抑制肿瘤生长，副作用较少。我们的研究结果为开发新型光激活钌（II）抗癌药物提供了指导。
