Acute Toxicity Evaluation of Non-Innocent Oxidovanadium(V) Schiff Base Complex

Abstract

The vanadium(V) complexes have been investigated as potential anticancer agents which makes it essential to evaluate their toxicity for safe use in the clinic. The large-scale synthesis and the acute oral toxicity in mice of the oxidovanadium(V) Schiff base catecholate complex, abbreviated as [VO(HSHED)dtb] containing a redox-active ligand with tridentate Schiff base (HSHED = N-(salicylideneaminato)-N’-(2-hydroxyethyl)-1,2-ethylenediamine) and dtb = 3,5-di-(t-butyl)catechol ligands were carried out. The body weight, food consumption, water intake as well biomarkers of liver and kidney toxicity of the [VO(HSHED)dtb] were compared to the precursors, sodium orthovanadate, and free ligand. The 10-fold scale-up synthesis of the oxidovanadium(V) complex resulting in the preparation of material in improved yield leading to 2–3 g (79%) material suitable for investigating the toxicity of vanadium complex. No evidence of toxicity was observed in animals when acutely exposed to a single dose of 300 mg/kg for 14 days. The toxicological results obtained with biochemical and hematological analyses did not show significant changes in kidney and liver parameters when compared with reference values. The low oral acute toxicity of the [VO(HSHED)dtb] is attributed to redox chemistry taking place under biological conditions combined with the hydrolytic stability of the oxidovanadium(V) complex. These results document the design of oxidovanadium(V) complexes that have low toxicity but still are antioxidant and anticancer agents.

Synthesis and characterization of two new mixed‐ligand Cu(II) complexes of a tridentate NN'O type Schiff base ligand and N‐donor heterocyclic co‐ligands: In vitro anticancer assay, DNA/human leukemia/COVID‐19 molecular docking studies, and pharmacophore modeling

“…Schiff base ligands and their transition metal complexes have played a great role in the design and development of metallodrugs. [1][2][3][4][5][6] These ligands and complexes are, to some extent, easily synthesized and their structural and electronic features could be smoothly tuned by the presence of various substituents. From a different point of view, mixed-ligand strategy also provides a new route to the synthesis of unique complexes with tuned stereo-electronic characteristics.…”

Tris(2-Pyridylmethylamine)V(O)2 Complexes as Counter Ions of Diprotonated Decavanadate Anion: Potential Antineoplastic Activity

“…As a result, numerous compounds based on decavanadate and cationic organic ligands have been published in recent years, which have been shown to lower blood sugar levels (Garcia-Vicente et al, 2007;Treviño et al, 2015;Treviño et al, 2018;, induce neuronal and cognitive restoration mechanisms while treating metabolic syndrome (Diaz et al, 2021), and inhibit the growth of protozoan parasites (Li et al, 2010;Silva-Nolasco et al, 2020). The cytotoxic or differentiating activity of oxidovanadium complexes with organic ligands against various cancer cell types is well known (Kioseoglou et al, 2015;Crans et al, 2018;Crans et al, 2019;Redher, 2020;Samart et al, 2020; Macedo Alves de Lima et al, 2021;Pessoa et al, 2021). However, their limited use in clinical trials is due to concerns about long-term toxicity caused by a lack of data, as well as complex speciation (ligand exchange and redox processes).…”

“…Nevertheless, a recent 300 mg/kg dose of [VO(HSHED)dtb] complex administration to mice showed no signs of toxicity. The complex was less toxic than orthovanadate salt, indicating that the compound was not broken down during administration ( Lima et al, 2021 ). The low toxicity is due to the redox properties obtained by coupling the redox-active ligand 3,5-di (tert-butyl)catechol with the hydrolytic stability of the [VO(HSHED)dtb], which prevents vanadate and catechol ligand formation.…”

Antitumor Properties of a New Macrocyclic Tetranuclear Oxidovanadium(V) Complex with 3-Methoxysalicylidenvaline Ligand

“…Different organic ligands or some molecules possessing biological properties such as amino acids-derived Schiff bases were used to develop new vanadium (IV or V) complexes with pharmacological properties [ 6 , 13 , 14 , 15 , 16 ]. The anti-tumor activity of vanadium(V) complexes with organic ligands that have the ability to chelate through donor atoms, such as O, N, O’/O, N, N’/O, O’/N, O has been reported [ 9 , 14 , 17 , 18 , 19 ]. Some of these compounds have been shown to induce reactive oxygen species (ROS)-mediated apoptosis [ 14 ].…”