Antiproliferative Activities of Diimine-Based Mixed Ligand Copper(II) Complexes

被引:37
作者
Kordestani, Nazanin [1 ]
Rudbari, Hadi Amiri [1 ]
Fernandes, Alexandra R. [2 ]
Raposo, Luis R. [2 ]
Baptista, Pedro, V [2 ]
Ferreira, Daniela [2 ]
Bruno, Giuseppe [3 ]
Bella, Giovanni [3 ]
Scopelliti, Rosario [4 ]
Braun, Jason [5 ]
Herbert, David E. [5 ]
Blacque, Olivier [6 ]
机构
[1] Univ Isfahan, Dept Chem, Esfahan 8174673441, Iran
[2] Univ Nova Lisboa, UCIBIO, Dept Ciencias Vida, Fac Ciencias & Tecnol, P-2829516 Caparica, Portugal
[3] Univ Messina, Dept Chem Biol Pharmaceut & Environm Sci, I-198166 Messina, Italy
[4] Ecole Polytech Fed Lausanne, Inst Sci & Ingn Chim, CH-1015 Lausanne, Switzerland
[5] Univ Manitoba, Dept Chem, Winnipeg, MB R3T 2N2, Canada
[6] Univ Zurich, Dept Chem, CH-8057 Zurich, Switzerland
关键词
copper(II); halogenated salicylaldehyde; mixed ligands; crystal structure; cytotoxicity; cancer; ovarian carcinoma cells; apoptosis; EFFICIENT CHEMICAL NUCLEASE; ANTI-PROLIFERATIVE ACTIVITY; DNA-BINDING PROPERTIES; PROTEIN-BINDING; MAGNETIC-PROPERTIES; OXIDATIVE CLEAVAGE; CRYSTAL-STRUCTURE; ANTICANCER; CYTOTOXICITY; TERPYRIDINE;
D O I
10.1021/acscombsci.9b00202
中图分类号
O69 [应用化学];
学科分类号
081704 ;
摘要
A series of Cu(diimine)(X-sal)(NO3) complexes, where the diimine is either 2,2'-bipyridine (bpy) or 1,10-phenanthroline (phen) and X-sal is a monoanionic halogenated salicylaldehyde (X = Cl, Br, I, or H), have been synthesized and characterized by elemental analysis and X-ray crystallography. Penta-coordinate geometries copper(II) were observed for all cases. The influence of the diimine coligands and different halogen atoms on the antiproliferative activities toward human cancer cell lines have been investigated. All Cu(II) complexes were able to induce a loss of A2780 ovarian carcinoma cell viability, with phen derivatives more active than bpy derivatives. In contrast, no in vitro antiproliferative effects were observed against the HCT116 colorectal cancer cell line. These cytotoxicity differences were not due to a different intracellular concentration of the complexes determined by inductively coupled plasma atomic emission spectroscopy. A small effect of different halogen substituents on the phenolic ring was observed, with X = Cl being the Most highly active toward A2780 cells among the phen derivatives, while X = Br presented the lowest IC50 in A2780 cells for bpy analogs. Importantly, no reduction in normal primary fibroblasts cell viability was observed in the presence of bpy derivatives (IC50 > 40 mu M). Mechanistically, complex 1 seems to induce a stronger apoptotic response with a higher increase in mitochondrial membrane depolarization and an increased level of intracellular reactive oxygen species (ROS) compared to complex 3. Together, these data and the low IC50 compared to cisplatin in A2780 ovarian carcinoma cell line demonstrate the potential of these bpy derivatives for further in vivo studies.
引用
收藏
页码:89 / 99
页数:11
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