Benzimidazole-quinoline-based copper complexes: Exploration for their possible antitumor mechanism

• DOI: 10.1016/j.poly.2021.115563
• Publication Date: 2021-11-02T06:59:53Z
• Authors: Jiyong Hu; Tingting Cao; Bangpeng Yuan; Yan Guo; Junshuai Zhang; Jin'an Zhao; Xuemin Zhao; Hongwei Hou
• Keywords: 0303 health sciences; 03 medical and health sciences; 3. Good health

Abstract In this study, we synthesised and characterised two benzimidazole-quinoline-based copper complexes, namely, [Cu(btmbq)Br]2 (1) and [Cu(btmbq)Cl]2 (2), (btmbq = 3-(1-(1H-benzotriazol-1-y-l)methyl)-6-bromo-1H-benzoimidazol-2-yl)isoquinoline). Both complexes showed strong antitumor abilities against the colon cancer cell line (HCT116) and low cytotoxicity against the normal liver cell line (L-02). The DNA binding affinity was evaluated using CD and fluorescence spectroscopy, and the Ksv and Kapp values were further quantified, revealing that the complexes bound to DNA in the intercalation mode, and caused oxidative damage to pBR322 DNA. Furthermore, complex 1 interfered with the steady-state balance of redox and Ca2+ in HCT116 cells, as well as induced cell mitochondrial membrane potential (Δψm) collapse, ATP dissipation, ultimately arrested the cell cycle in G2 phase and induced cell apoptosis. Further exploration demonstrated that the production of reactive oxygen species (ROS) might be the major contributors to the apoptotic death of HCT116 cells.