Department of Chemistry, Loyola College, Chennai, 600034, India.
Department of Chemistry, Sacred Heart College, Tirupattur, 635601, India.
J Biol Inorg Chem. 2018 Jul;23(5):833-848. doi: 10.1007/s00775-018-1579-z. Epub 2018 Jun 14.
The synthesis of the platinum(II) complexes, Pt(AIP)(bpy) (1) and Pt(PIP)(phen) (2), of anthracene- and pyrene-conjugated imidazophenanthroline ligands and their in vitro cytotoxicity toward the fibroblast cells and the HeLa cell lines are reported. MTT assay demonstrates their cytotoxicity against the HeLa cell lines with the IC values of 1.35 and 1.56 µM, respectively, and the cytotoxicity profiles indicate that the HeLa cell lines show more activity than the fibroblast cells. Trypan blue assay highlights significant damage on the HeLa cell lines with a pronounced reduction on their clonogenicity. AO/EB staining shows marked morphologic signs of apoptosis in a dose-dependent manner and the LDH and DNA laddering assays also lend support to the cytotoxicity of the complexes. The molecular docking study reveals that the complexes interact with DNA through hydrogen bonding. The TD-DFT energy-optimized structures of the complexes show that the platinum(II) center has a slightly distorted square-planar geometry. The TD-DFT modelled LUMOs receive major contributions from the platinum d-orbitals, while the HOMOs are delocalized largely on the anthracenyl- and pyrenyl ligands, resulting in the LMCT transition at 352 nm. The structural, bonding, electronic, and optical properties of the complexes 1 and 2 reported in the present work and that of Pt(AIP)(phen) (3) and Pt(PIP)(bpy) (4), reported by us recently, and the approved drugs cisplatin, carboplatin, and oxaliplatin are described in the light of the optimized geometries, ΔE, polarizability (α), hyperpolarizability (β), Mulliken negativities, and dipole moments computed from the ab initio and DFT computational studies. The synthesis of Pt(II) complexes of anthracene- and pyrene-appended imidazophenanthroline ligands and their in vitro cytotoxicity against fibroblast cells and HeLa cell lines are reported. The DFT computational study of the complexes and cisplatin, carboplatin, and oxaliplatin are described in search of the ligand design features for the development of new Pt-drugs.
本文报道了蒽和并五苯共轭咪唑二氮杂菲配体的铂（II）配合物[Pt（AIP）（bpy）]（PF）（1）和[Pt（PIP）（phen）]（PF）（2）的合成及其对成纤维细胞和 HeLa 细胞系的体外细胞毒性。MTT 试验表明，它们对 HeLa 细胞系的细胞毒性分别为 1.35 和 1.56 μM，细胞毒性谱表明 HeLa 细胞系比成纤维细胞系具有更高的活性。台盼蓝试验突出显示了 HeLa 细胞系的显著损伤，其克隆形成能力明显降低。AO/EB 染色以剂量依赖性方式显示出明显的凋亡形态学特征，LDH 和 DNA 梯状电泳试验也支持配合物的细胞毒性。分子对接研究表明，这些配合物通过氢键与 DNA 相互作用。配合物的 TD-DFT 能量优化结构表明，铂（II）中心具有轻微扭曲的正方形平面几何形状。TD-DFT 模拟的 LUMO 主要来自铂的 d 轨道，而 HOMO 则主要分布在蒽基和并五苯配体上，导致 352nm 处的 LMCT 跃迁。根据优化的几何形状、ΔE、极化率（α）、超极化率（β）、Mulliken 负电荷和从从头算和 DFT 计算研究中计算得出的偶极矩，描述了本工作中报道的配合物 1 和 2 以及我们最近报道的[Pt（AIP）（phen）]（PF）（3）和[Pt（PIP）（bpy）]（PF）（4）的结构、键合、电子和光学性质，以及批准的药物顺铂、卡铂和奥沙利铂。本文报道了蒽和并五苯衍生的咪唑二氮杂菲配体的铂（II）配合物的合成及其对成纤维细胞和 HeLa 细胞系的体外细胞毒性。描述了配合物与顺铂、卡铂和奥沙利铂的 DFT 计算研究，以寻找新的铂药物开发的配体设计特征。
