The anticancer potential of sixteen platinum(II) complexes with general formulae [PtCl(hq)(S-dmso)] (1a–8a) and [PtCl(hq)(pta)] (1b–8b) (where hq is 5-chloro-7-iodo-8-quinolinol (clioquinol; cqH) (1a, 1b), 8-hydroxy-5-nitroquinoline (nitroxoline; nxH) (2a, 2b), 5,7-dichloro-8-quinolinol (3a, 3b), 5,7-diiodo-8-quinolinol (4a, 4b), 5,7-dibromo-8-quinolinol (5a, 5b), 5,7-dichloro-8-hydroxy-2-methyl-quinoline (6a, 6b), 8-hydroxyquinoline (7a, 7b) and 8-quinolinethiol (8a, 8b); dmso is dimethyl sulfoxide and pta is 1,3,5-triaza-7-phosphaadamantane) was determined through in vitro cytotoxicity assay in human fibroblasts (MRC5) and two carcinoma cell lines (A375 and A549) and embryotoxicity assay in a zebrafish model. Interactions with double stranded DNA through in vitro assay and a molecular docking study were examined. All complexes, except 6a, exhibited a high cytotoxic effect on MRC5 cells at a concentration of 10 μg mL⁻¹ while 1b, 5a, 6a and 3b showed selective toxicity towards carcinoma cell lines. In general, pta-based complexes (series b) were more toxic according to the results of a MTT screen and the LC₅₀ values obtained in zebrafish (Danio rerio) assay; they also induced higher oxidative stress in this model. Successful cellular uptake of complexes was shown by the ICP-MS methodology. The binding propensity of the complex with DNA obtained in in silico studies can be correlated with those from the experimental investigation. Compounds with the highest binding potential, according to the interaction energy value, were 1b, 3b, 6b and 5b. From observations of the DNA interaction ability and of the in silico assessment, no apparent DNA fragmentation was observed either on DNA extracted from the treated cancer cell line or from the zebrafish embryos.

中文翻译：

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一类新的具有膦配体pta的铂（II）配合物，显示出有效的抗癌活性

16铂的抗癌潜力（II）与通式配合物[氯铂酸（HQ）（小号-DMSO）]（1A-8A）和[氯铂酸（HQ）（PTA）]（1B-8B）（其中HQ是5-氯-7-碘-8-喹啉（clioquinol; cqH）（1a，1b），8-羟基-5-硝基喹啉（nitroxoline; nxH）（2a，2b），5,7-二氯-8-喹啉（3a，3b），5,7-二碘-8-喹啉（4a，4b），5,7-二溴-8-喹啉（5a，5b），5,7-二氯-8-羟基-2-甲基喹啉（6a，6b），8-羟基喹啉（7a，7b）和8-喹啉硫醇（8a，8b）; dmso是二甲基亚砜，pta是1,3,5-triaza-7-phosphaadamantane）是通过在人成纤维细胞（MRC5）和两种癌细胞系（A375和A549）中进行体外细胞毒性测定，并在斑马鱼模型中进行胚胎毒性测定来确定的。通过体外测定和分子对接研究与双链DNA的相互作用进行了检查。除6a外，所有复合物均以10μgmL ^-1的浓度对MRC5细胞表现出高细胞毒性作用，而1b，5a，6a和3b表现出对癌细胞系的选择性毒性。一般而言，根据MTT筛选结果和斑马鱼（Danio rerio）测定的LC ₅₀值，基于pta的配合物（系列b）的毒性更大。他们在该模型中还诱导了更高的氧化应激。ICP-MS方法显示了复合物对细胞的成功吸收。在计算机研究中获得的复合物与DNA的结合倾向可以与实验研究的结果相关。根据相互作用能值，具有最高结合电位的化合物为1b，3b，6b和5b。从DNA相互作用能力和计算机评估的观察，在从经处理的癌细胞系或从斑马鱼胚胎中提取的DNA上均未观察到明显的DNA片段化。