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

Abstract

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 μM). 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.

The effect of halogenation of salicylaldehyde on the antiproliferative activities of {Δ/Λ-[Ru(bpy)2(X,Y-sal)]BF4} complexes

“…39 Recently we synthesized a series of Cu(diimine)(X,Y-sal) (NO 3 ) complexes, where the diimine is either bpy or phen, sal is salicylaldehyde, and X and Y are Cl, Br, I and H. The data set showed the potential of these bpy derivatives for further in vivo studies. 40 On the basis of these promising results, we synthesized such kinds of compounds with different metal ions. From the first attempt, based on the above description of the anticancer activity of the ruthenium compounds, we concluded on the one side that the ruthenium atom is the best alternative for the copper atom and, on the other side, the properties of the Ru(II)-bpy, Ru(II)-salicylaldehyde base derivatives and the introduction of halogens into the phenyl ring have prompted us to report the synthesis, structural characterization, and antibacterial and anticancer activity of this series of novel chiral {Δ/Λ-[Ru(bpy) 2 (X,Y-sal)]BF 4 } complexes (1)(2)(3)(4)(5), where X,Y-sal is monoanionic halogenated salicylaldehyde (X = Cl, Br and H; Y = Cl and Br).…”

“…Recently we synthesized a series of Cu(diimine)(X,Y-sal)(NO 3 ) complexes, where the diimine is either bpy or phen, sal is salicylaldehyde, and X and Y are Cl, Br, I and H. The data set showed the potential of these bpy derivatives for further in vivo studies. 40…”

Synthesis, Characterization and Anticancer Efficacy Studies of Iridium (III) Polypyridyl Complexes against Colon Cancer HCT116 Cells

“…Moreover, Ir1 showed a stronger ability to kill HCT116 cells than Ir2 . Comparing the IC 50 value with the cisplatin (IC 50 = 15.6 ± 0.4 µM) [ 36 ], the complexes show higher cytotoxic activity against HCT116 cells than the cisplatin and gold(III) porphyrin complex (Au(III)porphyrin-adamantane chloride) (IC 50 = 5.3 µM) [ 37 ]. The cytotoxic activity of Ir1 toward HCT116 cells is comparable with that of the ruthenium metal complex [Ru(phpy)(bpy) 2 ]Cl (phpy = 2-phenylpyridine, bpy = 2,2′-bipyridine, IC 50 = 1.6 ± 0.6 µM) [ 38 ].…”

In Vitro and In Vivo Effect of Palladacycles: Targeting A2780 Ovarian Carcinoma Cells and Modulation of Angiogenesis

“…Annexin V/PI labeling allows the identification of normal cells (no labeling), of cells in early apoptosis (Annexin V only labeling) and late apoptosis (Annexin V- and PI-labeled cells), and of cells in necrosis (PI-only labeled cells). , It is possible to observe that compound 3 induces an increase of apoptosis, 28.8% apoptotic cells compared to 1.9% in the DMSO control. Most apoptotic cells are in late apoptosis (24.4% of late apoptotic cells versus 0.4% in the DMSO control) after 48 h of exposure to the IC 50 concentration (Figure ).…”