Department of Chemistry, Faculty of Arts and Sciences, Uludag University, 16059 Bursa, Turkey.
Dalton Trans. 2018 Aug 21;47(33):11397-11410. doi: 10.1039/c8dt02389a.
New neutral [M(sac)2(diphos)] and cationic M(diphos)22 complexes, where M = PdII or PtII, 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.
新的中性 [M(sac)2(diphos)] 和阳离子 M(diphos)22 配合物，其中 M = PdII 或 PtII，sac = 糖酸盐，diphos = 1,1-双（二苯基膦基）甲烷 (dppm) 或 1,2-双（二苯基膦基）乙烷 (dppe)，被合成并进行了结构表征。研究了这些配合物对 MCF-7（乳腺）、A549（肺）、HCT116（结肠）、DU145（前列腺）癌症和 BEAS-2B（正常支气管上皮）细胞的抗癌活性。中性 Pt-dppm（2）和 Pd-dppe 配合物（5）没有显示出任何生物活性。阳离子 Pd-dppe（7）配合物显示出抗增殖活性，而其余的配合物与顺铂相比表现出很强的细胞毒性。然后将活性 Pd(ii)/Pt(ii)配合物纳入进一步的研究，包括与 DNA/HSA 的相互作用、核酸酶活性、细胞摄取和脂溶性。通过 Annexin V 阳性和半胱天冬酶激活来探测，有效的配合物诱导了细胞凋亡。对 HCT116 细胞的机制研究表明，这些配合物导致细胞周期停滞在 DNA 合成（S）期，并产生大量的活性氧物种（ROS），对线粒体和 DNA 都有损伤。
