Cytotoxicity activity, in silico molecular docking, protein- and DNA-binding study of a new Ni(II) Schiff base complex

One new nickel(II) complex, [Ni(L)] (<b>1</b>), was synthesized from the Schiff base ligand derived from pyrrole-2-carboxaldehyde and 1,3-diaminopropane. Complex <b>1</b> was characterized by elemental analysis, IR, UV-Vis and ESI mass spectroscopy, cyclic voltammetry, and single-crystal X-ray structure analysis. Crystallographic results show that two Ni(II) monomeric moieties are present with similar structural features but with slightly different bond lengths and bond angles. The geometry around the Ni(II) center is distorted square planar. DNA-binding properties of complex <b>1</b> were well explored by employing UV-Vis and fluorescence spectral methods, cyclic voltammetry, and by viscosity measurements. Similarly the protein-binding study was studied by multispectroscopic techniques using both BSA and HSA. The cytotoxicity study of the compound has also been evaluated. Notably, the in vitro cytotoxicity of complex <b>1</b> on two cancer cell lines (AGS and A549) demonstrates that complex <b>1</b> has very good anticancer activity. MTT assay, cell-cycle analysis, and annexin-V assay have been performed to know the extent of effect of complex <b>1</b> as anticancer agent. Further, in silico molecular docking study revealed that the nickel(II) complex fits into the minor groove of duplex DNA by hydrophobic interaction with functional groups of B-DNA.

本研究以吡咯-2-甲醛（pyrrole-2-carboxaldehyde）与1,3-丙二胺（1,3-diaminopropane）缩合得到的希夫碱（Schiff base）为配体，合成了一种新型镍(II)配合物[Ni(L)]（配合物1）。通过元素分析、红外光谱（IR）、紫外-可见光谱（UV-Vis）、电喷雾电离质谱（ESI mass spectroscopy）、循环伏安法以及单晶X射线衍射结构分析对配合物1进行了表征。晶体学分析结果显示，该配合物存在两个结构特征相似但键长与键角略有差异的镍(II)单核单元；镍(II)中心的配位几何为畸变的平面正方形构型。通过紫外-可见光谱、荧光光谱、循环伏安法以及黏度测定法，对配合物1与DNA的结合特性进行了系统探究。同样，采用多光谱技术分别以牛血清白蛋白（BSA）和人血清白蛋白（HSA）为模型蛋白，开展了配合物1与蛋白质的结合特性研究。此外，还对该配合物的细胞毒性进行了评价。值得注意的是，配合物1对两种癌细胞系（AGS和A549）的体外细胞毒性实验结果表明，其具备优异的抗癌活性。采用MTT法、细胞周期分析以及膜联蛋白V（annexin-V）实验，对配合物1作为抗癌剂的作用效果进行了深入表征。进一步的计算机辅助分子对接（in silico molecular docking）研究显示，该镍(II)配合物可通过与B型DNA（B-DNA）的官能团发生疏水相互作用，嵌入双链DNA的小沟区。