New neutral [M(sac)₂(diphos)] and cationic [M(diphos)₂](sac)₂ complexes, where M = Pd^II or Pt^II, sac = saccharinate, and diphos = 1,1-bis(diphenylphosphino)methane (dppm) or 1,2-bis(diphenylphosphino)ethane (dppe), were synthesized and structurally characterized. The anticancer activity of the complexes was investigated against MCF-7 (breast), A549 (lung), HCT116 (colon), DU145 (prostate) cancer and BEAS-2B (normal bronchial epithelial) cells. Neutral Pt-dppm (2) and Pd-dppe complexes (5) did not show any biological activity. The cationic Pd-dppe (7) complex displayed antiproliferative activity, while the rest of the complexes exhibited potent cytotoxicity compared with cisplatin. The active Pd(II)/Pt(II) complexes were then included in further studies including interaction with DNA/HSA, nuclease activity, cellular uptake and lipophilicity. The potent complexes induced the apoptotic cell death as probed through annexin V positivity and caspase activation. Mechanistic studies on HCT116 cells showed that the complexes cause cell cycle arrest at the DNA synthesis (S) phase and excessive generation of reactive oxygen species (ROS), damaging to both mitochondria and DNA.

中文翻译：

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糖精 钯（ii）和铂（ii）与双（二苯基膦基）甲烷/乙烷的复合物：人结肠癌细胞的合成，S期阻滞和ROS介导的细胞凋亡†

新的中性[M（sac）₂（diphos）]和阳离子[M（diphos _{2 2}）（sac）₂配合物，其中M = Pd ^II或Pt ^II，sac =糖精，而diphos = 1,1-双（二苯基膦基）合成甲烷）（dppm）或1,2-双（二苯基膦基）乙烷（dppe）并进行结构表征。研究了该复合物对MCF-7（乳腺癌），A549（肺癌），HCT116（结肠），DU145（前列腺）癌和BEAS-2B（正常支气管上皮）细胞的抗癌活性。中性Pt-dppm（2）和Pd-dppe复合物（5）没有显示任何生物活性。阳离子Pd-dppe（7）复合物具有抗增殖活性，而其余的复合物与顺铂相比具有强的细胞毒性。然后将活性Pd（II）/ Pt（II）复合物纳入进一步的研究中，包括与DNA / HSA的相互作用，核酸酶活性，细胞摄取和亲脂性。通过膜联蛋白V阳性和胱天蛋白酶激活探测到，有效的复合物诱导了凋亡细胞的死亡。对HCT116细胞的机理研究表明，该复合物会导致细胞周期停滞在DNA合成（S）阶段，并过多产生活性氧（ROS），从而破坏线粒体和DNA。