Effects of Metal Salophene and Saldach Complexes on Lymphoma and Leukemia Cells

Abstract

Schiff base transition metal complexes are an important class of compounds with great potential for therapeutic interventions. However, data on antileukemic and antilymphoma effects of these complexes are limited. The activity of N,N'-bis(salicylidene)-1,2-phenylenediamine (salophene, 1), its iron(II/III) and manganese(II/III) complexes as well as rac-trans-N,N'-bis(salicylidene)-1,2-cyclohexanediamine (saldach, 2) and its respective iron(II/III) complexes was evaluated against U-937 non-Hodgkin's lymphoma and the HL-60, SUP-B15, and K-562 leukemia cell lines. The free ligands induced in all cell lines, if at all, only marginal, concentration-dependent growth inhibitory effects, and did not trigger Cu/Zn superoxide dismutase (Cu/Zn SOD) release or induce apoptosis. [Fe(II) (salophene)] (3) and [Fe(III) (salophene)Cl] (4) blocked cellular growth, caused a strong release of Cu/Zn SOD and induced apoptosis. In contrast, the manganese analogs [Mn(II) (salophene)] (5) and [Mn(III) (salophene)OAc] (6) inhibited cell growth, caused the programmed cell death only at higher concentrations and did not provoke release of Cu/Zn SOD in any of the four cell lines. Weaker cell death-promoting effects were observed when the salophene moiety of 3 and 4 was replaced with saldach (complexes 7 and 8), indicating the influence exerted by the ligand structure. In conclusion, Schiff base transition metal complexes induce strong inhibitory effects on human lymphoma and leukemia cells.

Fluorinated Fe(III) Salophene Complexes: Optimization of Tumor Cell Specific Activity and Utilization of Fluorine Labeling for in Vitro Analysis

“…Induction of apoptosis is known to play a major role in the mechanism of action of metal-based anticancer drugs. In earlier investigations we demonstrated that the lead compound Fe III (salophene)Cl causes programmed cell death in U-937 and K-562 cells and that apoptosis is induced in a concentration-dependent manner in BJAB cells. Moreover, a significant loss of the mitochondrial membrane potential has been observed in lymphoma cells, indicating the involvement of the intrinsic mitochondrial pathway .…”

“…28−30 Concerning Fe(III) salophene complexes, the mode of action was already intensively investigated and it was demonstrated that cell death is caused by interference with more than one intracellular target. [13][14][15]31 However, to date, no information is available on the DNA binding properties of these complexes. Therefore, we were interested in analyzing the interactions of the novel Fe(III) complexes with isolated DNA.…”

“…DNA is generally believed to be the major biological target of cisplatin and other platinum-containing compounds . In the case of cisplatin, the cytotoxicity is attributed to the formation of 1,2-intrastrand cross-links between the N7 atoms of two adjacent purine residues and the resulting inhibition of transcription. , Interesting interactions with DNA were also observed for structurally related metal salen and salophene derivates (i.e., Fe(III) hydroxyl­salicylidene­ethylenediamines, Fe(III) salens, Mn(III) salen, and salophene derivatives), and DNA cleaving efficiency was found to be highly dependent on both the identity and position of the substituents. − Concerning Fe(III) salophene complexes, the mode of action was already intensively investigated and it was demonstrated that cell death is caused by interference with more than one intracellular target. − , However, to date, no information is available on the DNA binding properties of these complexes. Therefore, we were interested in analyzing the interactions of the novel Fe(III) complexes with isolated DNA.…”

A New Approach in Cancer Treatment: Discovery of Chlorido[N,N′-disalicylidene-1,2-phenylenediamine]iron(III) Complexes as Ferroptosis Inducers

“…Exponentially growing HL-60 cells were seeded into 6-well tissue culture plates at a concentration of 1 × 10 6 cells in 1400 μL of medium per well. The cell suspension was kept for 2 h at 37 °C in a 5% CO 2 /95% air atmosphere prior to the addition of 600 μL drug (10,16,18) or vehicle (DMSO) containing medium to end up with a final volume of 2000 μL and a concentration of 3 μM in each well. The plates were incubated for 1, 2, 4, and 6 h, respectively.…”

“…A promising class of candidates includes [ N , N ′-disalicylidene-1,2-diaminoethane]­metal complexes, mainly designed as catalysts. , During the past decade, the antitumor effects of many derivatives were described. , Their synthesis is straightforward, including a condensation reaction of an 1,2-diaminoethane moiety with salicylic aldehydes. If 1,2-diaminocyclohexane or 1,2-phenylenediamines are used, the metal complexes displayed partly outstanding antitumor properties. − Especially the chlorido­[ N , N ′-disalicylidene-1,2-phenylenediamine]­iron­(III) ( 10, Scheme ) was identified as a promising lead.…”