School of Chemistry, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, UK.
Department of Pharmacy, University of Huddersfield, Huddersfield, HD1 3DH, UK.
Chemistry. 2021 Feb 19;27(11):3737-3744. doi: 10.1002/chem.202004024. Epub 2021 Jan 19.
The synthesis and characterization of new bis(bipyridine)ruthenium(II) ferrocenyl β-diketonate complexes, [(bpy) Ru(Fc-acac)][PF ] (bpy=2,2'-bipyridine; Fc-acac=functionalized ferrocenyl β-diketonate ligand) are reported. Alongside clinical platinum drugs, these bimetallic ruthenium-iron complexes have been screened for their cytotoxicity against MIA PaCa-2 (human pancreatic carcinoma), HCT116 p53 (human colon carcinoma, p53-wild type) and ARPE-19 (human retinal pigment epithelial) cell lines. With the exception of one complex, the library exhibit nanomolar potency against cancerous cell lines, and their relative potencies are up to 40x, 400x and 72x more cytotoxic than cisplatin, carboplatin and oxaliplatin, respectively. Under hypoxic conditions, the complexes remain cytotoxic (sub-micromolar range), highlighting their potential in targeting hypoxic tumor regions. The Comet assay was used to determine their ability to damage DNA, and results show dose dependent damage which correlates well with the cytotoxicity results. Their potential to treat bacterial and fungal strains has been determined, and highlight complexes have selective growth inhibition of up to 87-100 % against Staphylococcus aureus and Candida albicans.
报告了新型双（联吡啶）钌（II）二茂铁基β-二酮配合物[（bpy）Ru（Fc-acac）][PF6]（bpy=2,2'-联吡啶；Fc-acac=功能化二茂铁基β-二酮配体）的合成与表征。这些双金属钌-铁配合物与临床铂类药物一起，对 MIA PaCa-2（人胰腺癌细胞）、HCT116 p53（人结肠癌细胞，p53-野生型）和 ARPE-19（人视网膜色素上皮细胞）细胞系进行了细胞毒性筛选。除了一个配合物外，该配合物库对癌细胞系具有纳摩尔效力，其相对效力分别比顺铂、卡铂和奥沙利铂高 40 倍、400 倍和 72 倍。在缺氧条件下，这些配合物仍具有细胞毒性（亚微摩尔范围），突出了它们在靶向缺氧肿瘤区域方面的潜力。彗星试验用于测定它们损伤 DNA 的能力，结果表明剂量依赖性损伤与细胞毒性结果很好地相关。还确定了它们治疗细菌和真菌菌株的潜力，突出了这些配合物对金黄色葡萄球菌和白色念珠菌的选择性生长抑制高达 87-100%。
