Department of Chemistry, Aligarh Muslim University, Aligarh, India.
Cytogenetics and Molecular Toxicology Laboratory, Section of Genetics, Department of Zoology, Aligarh Muslim University, Aligarh 202002, Uttar Pradesh, India.
Dalton Trans. 2022 Aug 9;51(31):11713-11729. doi: 10.1039/d2dt01312f.
To validate the effect of metal ions in analogous ligand scaffolds on DNA binding and cytotoxic response, we have synthesized a series of water-soluble ionic -phthaloylglycinate conjugated bis(diaminocyclohexane)M complexes where M = Ni(II), Cu(II) and Zn(II) (1-3). The structural characterization of the complexes (1-3) was achieved by spectroscopic {FT-IR, EPR, UV-vis absorption data, H NMR, ESI-MS and elemental analysis} and single crystal X-ray diffraction studies, which revealed different topologies for the late 3d-transition metals. The Ni(II) and Zn(II) complexes exhibited an octahedral geometry with coordinated labile water molecules in the 1̄ space group while the Cu(II) complex revealed a square planar geometry with the 2/ space lattice. DNA-complexation studies were performed employing various complementary biophysical methods to quantify the intrinsic binding constant and values and to envisage the binding modes and binding affinity of (1-3) at the therapeutic targets. The corroborative results of these experiments revealed a substantial geometric and electronic effect of (1-3) on DNA binding and the following inferences were observed, (i) high and values, (ii) remarkable cleavage efficiency an oxidative pathway, (iii) condensation behavior and (iv) good cytotoxic response to HepG2 and PTEN-caP8 cancer cell lines, with copper(II) complex 2 outperforming the other two complexes as a most promising anticancer drug candidate. Copper(II) complexes have been proven in the literature to be good anticancer drug entities, displaying inhibition of uncontrolled-cell growth by multiple pathways , anti-angiogenesis, inducing apoptosis and reactive oxygen species mediated cell death phenomena. Nickel(II) and zinc(II) ionic complexes 1 and 3 have also demonstrated good chemotherapeutic potential and the bioactive 1,2-diaminocyclohexane fragment in these complexes plays an instrumental role in anticancer activity.
为了验证类似配体支架中的金属离子对 DNA 结合和细胞毒性反应的影响，我们合成了一系列水溶性离子-邻苯二甲酰基甘氨酸共轭双（二氨基环己烷）M 配合物，其中 M = Ni(II)、Cu(II)和 Zn(II)（1-3）。通过光谱（FT-IR、EPR、UV-vis 吸收数据、H NMR、ESI-MS 和元素分析）和单晶 X 射线衍射研究对配合物（1-3）进行了结构表征，揭示了 3d 过渡金属的不同拓扑结构。Ni(II)和 Zn(II)配合物表现出八面体几何形状，在 1̄空间群中具有配位的可移动水分子，而 Cu(II)配合物呈现出正方形平面几何形状，晶格为 2/。通过各种互补的生物物理方法进行 DNA 配位研究，以定量测量固有结合常数 和 值，并设想（1-3）在治疗靶标上的结合模式和结合亲和力。这些实验的综合结果表明，（1-3）对 DNA 结合具有显著的几何和电子效应，并且观察到以下推论：（i）高 和 值，（ii）显著的切割效率（氧化途径），（iii）缩合行为和（iv）对 HepG2 和 PTEN-caP8 癌细胞系的良好细胞毒性反应，其中铜（II）配合物 2 作为最有前途的抗癌药物候选物表现优于其他两种配合物。文献中已经证明铜（II）配合物是良好的抗癌药物实体，通过多种途径抑制不受控制的细胞生长、抗血管生成、诱导细胞凋亡和活性氧介导的细胞死亡现象。镍（II）和锌（II）离子配合物 1 和 3 也表现出良好的化学治疗潜力，并且这些配合物中的生物活性 1,2-二氨基环己烷片段在抗癌活性中发挥着重要作用。
