School of Chemistry, University of Sydney, Sydney, NSW, Australia.
School of Chemistry, University of Sydney, Sydney, NSW, Australia.
J Inorg Biochem. 2018 Feb;179:146-153. doi: 10.1016/j.jinorgbio.2017.11.018. Epub 2017 Nov 22.
CHS-828 (N-(6-(4-chlorophenoxy)hexyl)-N'-cyano-N″-4-pyridyl guanidine) is an anticancer agent with low bioavailability and high systemic toxicity. Here we present an approach to improve the therapeutic profile of the drug using photolabile ruthenium complexes to generate light-activated prodrugs of CHS-828. Both prodrug complexes are stable in the dark but release CHS-828 when irradiated with visible light. The complexes are water-soluble and accumulate in tumour cells in very high concentrations, predominantly in the mitochondria. Both prodrug complexes are significantly less cyototoxic than free CHS-828 in the dark but their toxicity increases up to 10-fold in combination with visible light. The cellular responses to light treatment are consistent with release of the cytotoxic CHS-828 ligand.
CHS-828（N-（6-（4-氯苯氧基）己基）-N'-氰基-N″-4-吡啶基胍）是一种抗癌药物，具有生物利用度低和全身毒性高的特点。在这里，我们提出了一种使用光不稳定钌配合物来提高药物治疗效果的方法，以生成 CHS-828 的光激活前药。两种前药配合物在黑暗中都很稳定，但在可见光照射下释放 CHS-828。这些配合物具有水溶性，并以非常高的浓度（主要在线粒体中）积累在肿瘤细胞中。与游离 CHS-828 相比，两种前药配合物在黑暗中的细胞毒性都明显降低，但与可见光结合后，其毒性增加了 10 倍。细胞对光处理的反应与释放细胞毒性 CHS-828 配体一致。
