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首页> 外文期刊>Dalton transactions: An international journal of inorganic chemistry >Mechanistic insights into a novel chromone-appended Cu(II) anticancer drug entity: in vitro binding profile with DNA/RNA substrates and cytotoxic activity against MCF-7 and HepG2 cancer cells
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Mechanistic insights into a novel chromone-appended Cu(II) anticancer drug entity: in vitro binding profile with DNA/RNA substrates and cytotoxic activity against MCF-7 and HepG2 cancer cells

机译：对新型色酮附加的Cu（II）抗癌药物实体的机理见解：与DNA / RNA底物的体外结合情况以及对MCF-7和HepG2癌细胞的细胞毒活性

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A new chromone-appended Cu(II) drug entity (1) was designed and synthesized as a potential anticancer chemotherapeutic agent. The structural elucidation was carried out thoroughly by elemental analysis, FT-IR, EPR, ESI-MS and single crystal X-ray crystallography. Complex 1 resulted from the in situ methoxylation reaction of the 3-formylchromone ligand and its subsequent complexation with the copper nitrate salt in a 2 : 1 ratio, respectively. 1 crystallized in the monoclinic P2(1)/c space group possessing the lattice parameters, a = 8.75 angstrom, b = 5.07 angstrom, c = 26.22 angstrom, alpha = gamma = 90 degrees, beta = 96.3 degrees per unit cell. Furthermore, in vitro interaction studies of 1 with ct-DNA and tRNA were carried out which suggested more avid binding propensity towards the RNA target via intercalative mode, which was reflected from its K-b, K and K-sv values. The gel electrophoretic mobility assay was carried out on the pBR322 plasmid DNA substrate, to ascertain the cleaving ability and the mechanistic pathway in the presence of additives, and the results revealed the efficient cleaving ability of 1 via the oxidative pathway. In vitro cell growth inhibition via the MTT assay was carried out to evaluate the cytotoxicity of complex 1 and IC50 values were found to be in the range of 5-10 mu g mL(-1) in HepG2 and MCF-7 cancer cell lines, which were found to be much lower than the IC50 values of previously reported similar Cu(II) complexes. Additionally, in the presence of 1, reactive oxygen species (ROS) and thiobarbituric acid reactive substance (TBARS) levels in the tested cancer cell lines increased significantly, coupled with reduced glutathione (GSH) levels. Thus, our results suggested that ROS plays an important role in cell apoptosis induced by the Cu(II) complex 1 and validates its potential to act as a robust anticancer drug entity.
机译：设计并合成了一种新的附加色酮的Cu（II）药物实体（1），作为潜在的抗癌化学治疗剂。通过元素分析，FT-IR，EPR，ESI-MS和单晶X射线晶体学彻底进行了结构阐明。配合物1是由3-甲酰基色酮配体的原位甲氧基化反应及其随后分别与硝酸铜盐以2∶1的比例配合而产生的。 1在具有晶格参数的单斜晶P2（1）/ c空间群中结晶，a =每单位晶胞a = 8.75埃，b = 5.07埃，c = 26.22埃，α=伽马= 90度，β= 96.3度。此外，进行了1与ct-DNA和tRNA的体外相互作用研究，结果表明其通过插入模式对RNA靶标具有更强烈的结合倾向，这从其K-b，K和K-sv值反映出来。在pBR322质粒DNA底物上进行了凝胶电泳迁移率测定，以确定在存在添加剂的情况下的裂解能力和机理途径，结果揭示了通过氧化途径对1的有效裂解能力。通过MTT分析进行体外细胞生长抑制以评估复合物1的细胞毒性，发现HepG2和MCF-7癌细胞系的IC50值在5-10μg mL（-1）范围内，被发现比以前报道的类似的Cu（II）配合物的IC50值低得多。另外，在存在1的情况下，被测癌细胞系中的活性氧（ROS）和硫代巴比妥酸反应性物质（TBARS）含量显着增加，同时谷胱甘肽（GSH）含量降低。因此，我们的结果表明，ROS在由Cu（II）配合物1诱导的细胞凋亡中起着重要作用，并验证了其作为强大的抗癌药物实体的潜力。

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