Dinuclear platinum(II) complexes of imidazophenanthroline-based bridging ligands as potential anticancer agents: synthesis, characterization, and in vitro cytotoxicity studies
Dinuclear platinum(II) complexes of imidazophenanthroline-based bridging ligands as potential anticancer agents: synthesis, characterization, and in vitro cytotoxicity studies
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DOI：
10.1007/s00775-019-01656-3
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发表时间：
2019-05-01
影响因子：
3
通讯作者：
Samy, N. Arockia
中科院分区：
文献类型：
--
作者：
Alexander, Carlson;Prajith, N. U.;Samy, N. Arockia
双核配体1，2-二的合成与表征（2-（1H-咪唑并[4，5-f][1，10]菲咯啉-2-基）苯氧基）乙烷（L1）和1，2-双（2-（1H-咪唑并[4，5-f][1，[10]菲咯啉-2-基）苯氧基）己烷（L2）及其双核配合物[Pt-2（L1）Cl-4]（1）和[Pt-2（L2）Cl-4]（2）的体外细胞毒性，HepG 2和MCF-7细胞系。配体L1在正交晶系中结晶，空间群为Pbca。配合物1和2的水合反应遵循一级动力学。MTT和台盼蓝试验表明，与顺铂相比，复合物对HepG 2和MCF-7细胞系的细胞毒性更高。AO/EB分析和通过Annexin V alexa fluor（（R））488/PI双染色分析的流式细胞术显示了以剂量依赖性方式的凋亡的明显形态学变化。细胞周期分析表明，随着复合物浓度的增加，G 0/G1期DNA含量显著减少，G2/M期DNA含量增加。复合物作为抗癌剂的潜力通过其对细胞系的抗增殖活性来证明。配合物1通过咪唑N-H质子与核苷酸残基DC`21/N4（胞嘧啶）之间的氢键作用，配合物2通过咪唑N-H质子与核苷酸残基DT`7/O2（胸腺嘧啶）和DT`19/O2（胸腺嘧啶）之间的氢键作用，结合能分别为-1.98和-4.45kcal/mol。[图片]
The synthesis and characterization of the dinucleating ligands 1,2-bis(2-(1H-imidazo[4,5-f][1,10]phenanthrolin-2-yl)phenoxy)ethane (L1) and 1,2-bis(2-(1H-imidazo[4,5-f][1, 10]phenanthrolin-2-yl)phenoxy)hexane (L2) and their dinuclear complexes [Pt-2(L1)Cl-4] (1) and [Pt-2(L2)Cl-4] (2) and the in vitro cytotoxicity of the complexes against HeLa, HepG2, and MCF-7 cell lines are reported. Ligand L1 crystallizes in the orthorhombic system with the space group Pbca. The complexes 1 and 2 undergo aquation following first-order kinetics. The MTT and trypan blue assays indicate higher cytotoxicity of the complexes towards the HepG2 and MCF-7 cell lines compared to cisplatin. The AO/EB assay and flow cytometry by Annexin V alexa fluor((R))488/PI double staining assay demonstrate distinct morphological changes of apoptosis in a dose dependent manner. The cell cycle analysis shows a marked decrease in the DNA content in the G0/G1 phase with an increase in the G2/M phase on increasing the concentration of the complexes. The potential of the complexes as anticancer agents is demonstrated by their antiproliferative activity on the cell lines. The complexes interact with the major groove of DNA through H-bonding between the imidazole N-H protons and the nucleotide residues DC`21/N4 (cytosine) for complex 1 and DT`7/O2 (thymine) and DT`19/O2 (thymine) for complex 2, with the binding energy of -1.98 and -4.45kcal/mol, respectively.[GRAPHICS]