Department of Inorganic Chemistry, Faculty of Science, Palacky University, 17. listopadu 12, CZ-771 46 Olomouc, Czech Republic.
Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, CZ-613 00 Brno, Czech Republic; Central European Institute of Technology, Brno University of Technology, Purkynova 656/123, CZ-612 00 Brno, Czech Republic.
J Inorg Biochem. 2021 Apr;217:111395. doi: 10.1016/j.jinorgbio.2021.111395. Epub 2021 Feb 12.
In the present study, nickel(II) complex with 2-[2-[2-(1H-benzimidazol-2-yl)ethylsulfanyl]ethyl]-1H-benzimidazole (tebb) of formula Ni(tebb) has been prepared and its structure was proved by X-ray crystallography. The central nickel atom is in deformed octahedral vicinity. Four nitrogen atoms of two ligands form plane of octahedral and sulfur atoms are in apical positions. Perchlorate anions are outside the coordination sphere. The coordination compound was tested for its biological activities in an array of in vitro assays. It was found that the synthesized complex possesses interesting biological activity, which is most likely related to its cell-type related uptake kinetics. The synthesized complex is readily uptaken by malignant MDA-MB-231 and CACO-2 cells with the lowest uptake by healthy Hs27 fibroblasts. The lowest IC values were obtained for MDA-MB-231 cells (5.2-12.7 μM), highlighting exceptional differential cytotoxicity (IC values for healthy fibroblasts were 38.6-51.5 μM). Furthermore, it was found the complex is capable to cause hydrolytic DNA cleavage, promotes an efficient DNA fragmentation and to trigger an extensive formation of intracellular reactive oxygen species. Overall, current work presents a synthesis of Ni(II) coordination compound with interesting biological behavior and with a promising potential to be further tested in pre-clinical models.
在本研究中，制备了化学式为Ni(tebb)的镍(II)配合物与 2-[2-[2-(1H-苯并咪唑-2-基)乙基硫代]乙基]-1H-苯并咪唑(tebb)，并通过 X 射线晶体学证明了其结构。中心镍原子处于变形的八面体近邻。两个配体的四个氮原子形成八面体平面，硫原子处于顶点位置。高氯酸根阴离子位于配位球体外。该配位化合物在一系列体外测定中进行了生物活性测试。结果发现，合成的配合物具有有趣的生物活性，这很可能与其细胞类型相关的摄取动力学有关。合成的配合物很容易被恶性 MDA-MB-231 和 CACO-2 细胞摄取，而健康的 Hs27 成纤维细胞摄取量最低。对 MDA-MB-231 细胞获得的最低 IC 值（5.2-12.7 μM），突出了异常的细胞毒性差异（健康成纤维细胞的 IC 值为 38.6-51.5 μM）。此外，还发现该配合物能够引起水解 DNA 断裂，促进有效的 DNA 片段化，并引发大量细胞内活性氧的形成。总的来说，目前的工作提出了一种具有有趣生物学行为的 Ni(II)配合物的合成，并具有在临床前模型中进一步测试的广阔前景。
