Post-Graduate and Research Department of Chemistry, The New College (Autonomous) , University of Madras , Chennai 600 014 , India.
Molecular Pharmacology and Pathology Program, Department of Pathology, Bosch Institute , University of Sydney , Sydney , New South Wales 2006 , Australia.
Chem Res Toxicol. 2019 Aug 19;32(8):1554-1571. doi: 10.1021/acs.chemrestox.9b00087. Epub 2019 Jul 8.
Eight heteroleptic nickel(II) and copper(II) complexes of the type [M(L)(nap)] (-), where L = 2-(1-(4-substitutedphenyl)ethylidene)hydrazinecarbothioamide, nap = naproxen, and M = Ni(II) or Cu(II), have been synthesized and characterized. UV-vis and EPR spectral studies showed distorted octahedral geometry around metal(II) ions. The cyclic voltammogram of complexes - displayed an irreversible one-electron transfer process in the cathodic region ( = -0.66 to -1.43 V), and nickel(II) complexes - displayed an irreversible one-electron oxidation process in the anodic region ( = 0.75 to 1.10 V). The obtained magnetic moment values (1.82-1.93 μ) for copper(II) complexes - indicate distortion from octahedral geometry, which is further supported by EPR studies. The geometry of the complexes is retained in both solid and solution phases as evidenced from UV-vis and EPR studies. All the complexes showed stability for almost 72 h in biologically relevant solutions. The reducing ability of the copper(II) complexes in the presence of ascorbic acid was analyzed by UV-vis and cyclic voltammetry techniques, which indicates the reduction of the copper(II) to a copper(I) center, and possible interaction within the cells. An antiproliferative study revealed the nontoxic nature of complexes to normal human dermal fibroblast (NHDF) up to a concentration of 100 ng/mL. The antiproliferative activity of the complexes was tested against three cancerous (human breast adenocarcinoma (MCF-7), hepatoma (HepG2), and lung (A549)) cell lines using MTT reduction assay, which showed enhanced activity for complexes and containing the hydrophobic substituent. Apoptotic and cellular uptake studies showed that complex is readily taken up by HepG2 cell lines and induces ROS-mediated mitochondrial and caspase-dependent apoptosis. studies indicated hydrogen bonding, hydrophobic, and π-pair (π-π, π-σ, and π-cation) interactions between the complexes and EGFR/VEGFR2 kinase receptors.
已合成并表征了 8 种异核镍(II)和铜(II)配合物，其通式为 [M(L)(nap)] (-)，其中 L = 2-(1-(4-取代苯基)亚乙基)腙硫代甲酰胺，nap = 萘普生，M = Ni(II)或 Cu(II)。UV-vis 和 EPR 光谱研究表明金属(II)离子周围存在扭曲的八面体几何形状。配合物-的循环伏安图在阴极区域显示出不可逆的单电子转移过程（= -0.66 至 -1.43 V），而镍(II)配合物-在阳极区域显示出不可逆的单电子氧化过程（= 0.75 至 1.10 V）。铜(II)配合物-获得的磁矩值（1.82-1.93 μ）表明存在从八面体几何形状的扭曲，这进一步得到了 EPR 研究的支持。从 UV-vis 和 EPR 研究中可以看出，配合物的几何形状在固态和溶液相中均得到保留。所有配合物在生物相关溶液中几乎稳定 72 小时。通过 UV-vis 和循环伏安法技术分析了铜(II)配合物在抗坏血酸存在下的还原能力，这表明铜(II)还原为铜(I)中心，并且在细胞内可能发生相互作用。细胞增殖抑制研究表明，配合物对正常人类皮肤成纤维细胞（NHDF）的毒性在 100 ng/mL 浓度以下呈非毒性。通过 MTT 还原测定法测试了配合物对三种癌细胞（人乳腺癌（MCF-7）、肝癌（HepG2）和肺癌（A549））的增殖抑制活性，结果表明含有疏水性取代基的配合物 和 表现出增强的活性。细胞凋亡和细胞摄取研究表明，配合物 易于被 HepG2 细胞系摄取，并诱导 ROS 介导的线粒体和 caspase 依赖性细胞凋亡。研究表明，配合物与 EGFR/VEGFR2 激酶受体之间存在氢键、疏水和 π-对（π-π、π-σ 和 π-阳离子）相互作用。
