配合物 [Cu(PI)2(H2O)](NO3)2 (1)、[Cu(PBI)2(NO3)]NO3 (2)、[Cu(TBI)2(NO3)]NO3 (3)、[ Cu(BBIP)2](ClO4)2 (4) 和 [Cu(BBIP)(CH3OH)(ClO4)2] (5) 由 Cu(II) 盐与 2-(2'-吡啶基) 反应合成咪唑 (PI)、(2-(2'-吡啶基)苯并咪唑 (PBI)、2-(4'-噻唑基)-苯并咪唑 (TBI)、2,6-双(苯并咪唑-2-基)-吡啶 (BBIP)使用顺铂作为阳性对照，分别测定了它们的组成和晶体结构，并在四种癌细胞系和一种正常细胞系（HL-7702）上筛选了它们的体外抗肿瘤活性。其他三种配合物的细胞毒性与顺铂相当，而4的细胞毒性远高于顺铂，从抗肿瘤的角度来看，2可能是T24肿瘤细胞系的一个不错的选择。 T24 和 HL-7702 上的 IC50 值分别为 15.03 ± 1.10 和 21.34 ± 0.35 因此，对 T24 细胞上的复合物 2 和 4 进行了机理研究。研究表明，它们可以降低线粒体膜电位，增加线粒体膜通透性，导致细胞内ROS水平增加、Ca2+内流、线粒体功能障碍，最终导致细胞凋亡。总之，它们可以通过线粒体功能障碍诱导细胞凋亡。这些发现可能有助于开发新的抗肿瘤药物。版权所有 © 2024 Elsevier Inc. 保留所有权利。

Complexes [Cu(PI)2(H2O)](NO3)2 (1), [Cu(PBI)2(NO3)]NO3 (2), [Cu(TBI)2(NO3)]NO3 (3), [Cu(BBIP)2](ClO4)2 (4) and [Cu(BBIP)(CH3OH)(ClO4)2] (5) were synthesized from the reactions of Cu(II) salts with 2-(2'-pyridyl)imidazole (PI), (2-(2'-pyridyl)benzimidazole (PBI), 2-(4'-thiazolyl)-benzimidazole (TBI), 2,6-bis(benzimidazol-2-yl)-pyridine (BBIP), respectively. Their compositions and crystal structures were determined. Their in-vitro antitumor activities were screened on four cancer cell lines and one normal cell line (HL-7702) using cisplatin as the positive control. Complexes 2 and 4 show higher cytotoxicity than the other three complexes. The cytotoxicity of complex 2 are comparable to those for cisplatin, and the cytotoxicity for 4 are much higher than those for cisplatin. From a viewpoint of antitumor, 2 might be a nice choice on the tumor cell line of T24 because its IC50 values on T24 and HL-7702 are 15.03 ± 1.10 and 21.34 ± 0.35, respectively. Thus, a mechanistic study for complexes 2 and 4 on T24 cells was conducted. It revealed that they can reduce mitochondrial membrane potential and increase mitochondrial membrane permeability, resulting in increased intracellular ROS levels, Ca2+ inward flow, dysfunctional mitochondria and the eventual cell apoptosis. In conclusion, they can induce cell apoptosis through mitochondrial dysfunction. These findings could be useful in the development of new antitumor agents.Copyright © 2024 Elsevier Inc. All rights reserved.