用于治疗应用的新型螯合剂的设计一直是解决各种疾病的广泛研究的主题。许多螯合剂可以操纵细胞内金属离子的水平并有效调节金属过量。在某些情况下，螯合剂对细胞表现出显着的毒性。我们通过电位测定法和紫外-可见光谱研究了聚咪唑配体形成铜(II)络合物的能力。我们还比较了聚咪唑配体及其铜 (II) 配合物与聚吡啶配体在 CaCo-2（结直肠腺癌）、SH-SY5Y（神经母细胞瘤）和 K562（慢性粒细胞白血病）细胞和正常 HaCaT（角质形成细胞）细胞中的抗增殖活性。聚咪唑配体的细胞毒性低于其类似的聚吡啶配体。除K562细胞的四咪唑配体外，所有聚咪唑配体对癌症和正常细胞的活力均未表现出任何显着影响。相比之下，在正常细胞中也观察到聚吡啶配体的细胞毒活性，其IC50值与癌细胞相似。四咪唑配体是唯一对白血病 K562 细胞系有活性的配体，可诱导 caspase 依赖性细胞凋亡，并增加细胞内活性氧的产生并导致线粒体损伤。聚咪唑配体的低细胞毒性，即使限制了它们作为抗癌药物的用途，也可以使其在其他医疗应用中发挥作用，例如治疗金属超载、微生物感染、炎症或神经退行性疾病。版权所有 © 2024。出版者爱思唯尔公司

The design of novel chelators for therapeutic applications has been the subject of extensive research to address various diseases. Many chelators can manipulate the levels of metal ions within cells and effectively modulate the metal excess. In some cases, chelators show significant toxicity to cells. We investigated polyimidazole ligands by potentiometry and UV-Vis spectroscopy for their ability to form copper(II) complexes. We also compared the antiproliferative activity of the polyimidazole ligands and their copper(II) complexes with polypyridine ligands in CaCo-2 (colorectal adenocarcinoma), SH-SY5Y (neuroblastoma) and K562 (chronic myelogenous leukemia) cells and normal HaCaT (keratinocyte) cells. Polyimidazole ligands are less cytotoxic than their analogous polypyridine ligands. All polyimidazole ligands, except the tetraimidazole ligand for K562 cells, did not show any significant effect on the viability of cancer and normal cells. In contrast, the cytotoxic activity of polypiridine ligands was also observed in normal cells with IC50 values similar to those of cancer cells. Tetraimidazole ligand, the only ligand active on the leukemic K562 cell line, induced caspase-dependent apoptosis and increased intracellular reactive oxygen species production with mitochondrial damage. The low cytotoxicity of the polyimidazole ligands, even if it limits their use as anticancer agents, could make them useful in other medical applications, such as in the treatment of metal overload, microbial infections, inflammation or neurodegenerative disorders.Copyright © 2024. Published by Elsevier Inc.