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

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.

Antimicrobial activity and cytotoxicity of transition metal carboxylates derived from agaric acid

Carboxylato-type transition metal complexes with agaric acid, a bioactive natural compound derived from citric acid, were prepared, and tested in vitro for their antimicrobial activity and cytotoxicity. The products as well as agaric acid itself are amphiphilic compounds containing a hydrophilic head (citric acid moiety) and a hydrophobic tail (non-polar alkyl chain). The putative composition of the carboxylates was assigned on grounds of elemental analysis, infrared (IR) and high-resolution mass spectra (HR-MS), as well as in analogy with known complexes containing the citrate moiety. The metal carboxylates showed interesting activity in several microbial strains, especially against S. aureus (vanadium complex; MIC = 0.05 mg/ml). They were also tested for their cytotoxic activity in hepatocytes, the highest activity having been found in the copper(II) and manganese(II) complexes. Further research based on these preliminary results is needed in order to evaluate the influence of parameters like stability of the metal complexes in solution on the bioactivity of the complexes.

Anti-hyperglycaemic effects of dioxidovanadium complex cis-[VO2(obz)py] avert kidney dysfunction in streptozotocin-induced diabetic male Sprague–Dawley rats

Despite the success of antidiabetic drugs in alleviation of hyperglycaemia, diabetic complications, including renal dysfunction, continue to be a burden. This raises the need to seek alternative therapies that will alleviate these complications. Accordingly, the aim of this study was to investigate the effects of dioxidovanadium(V) complex cis-[VO2(obz)py] on renal function in diabetic rats. Streptozotocin-induced diabetic rats were treated with cis-[VO2(obz)py] (40 mg·kg–1) twice every third day for five weeks. Diabetic untreated and insulin-treated rats served as the diabetic control and positive control, respectively. Blood glucose concentrations, water intake, urinary output, and mean arterial pressure (MAP) were monitored weekly for five weeks. Rats were then euthanized, and blood and kidney tissues were collected for biochemical analysis. Significant decreases in blood glucose concentrations, MAP, glomerular filtration rate (GFR), and SGLT2 expression, as well as plasma angiotensin and aldosterone concentrations, were observed in the treated groups compared with the diabetic control. The complex also increased urinary glucose concentrations, antioxidant enzymes GPx and SOD concentrations, and decreased MDA concentrations and kidney injury molecule (KIM-1) concentrations. These findings suggest that the anti-hyperglycaemic effects of this vanadium complex may ameliorate kidney dysfunction in diabetes.

Selective Cytotoxicity of Complexes with N,N,N-Donor Dipodal Ligand in Tumor Cells

The present article demonstrates selective cytotoxicity against cancer cells of the complexes [Co(LD)2]I2∙CH3OH (1), [CoLD(NCS)2] (2) and [VOLD(NCS)2]∙C6H5CH3 (3) containing the dipodal tridentate ligand LD = N,N-bis(3,5-dimethylpyrazol-1-ylmethyl)amine), formed in situ. All tested complexes expressed greater anticancer activities and were less toxic towards noncancerous cells than cisplatin. Cobalt complexes (1 and 2) combined high cytotoxicity with selectivity towards cancer cells and caused massive tumour cell death. The vanadium complex (3) induced apoptosis specifically in cancer cells and targeted proteins, controlling their invasive and metastatic properties. The presented experimental data and computational prediction of drug ability of coordination compounds may be helpful for designing novel and less toxic metal-based anticancer species with high specificities towards tumour cells.

Misinterpretations in Evaluating Interactions of Vanadium Complexes with Proteins and Other Biological Targets

In aqueous media, VIV- and VV-ions and compounds undergo chemical changes such as hydrolysis, ligand exchange and redox reactions that depend on pH and concentration of the vanadium species, and on the nature of the several components present. In particular, the behaviour of vanadium compounds in biological fluids depends on their environment and on concentration of the many potential ligands present. However, when reporting the biological action of a particular complex, often the possibility of chemical changes occurring has been neglected, and the modifications of the complex added are not taken into account. In this work, we highlight that as soon as most vanadium(IV) and vanadium(V) compounds are dissolved in a biological media, they undergo several types of chemical transformations, and these changes are particularly extensive at the low concentrations normally used in biological experiments. We also emphasize that in case of a biochemical interaction or effect, to determine binding constants or the active species and/or propose mechanisms of action, it is essential to evaluate its speciation in the media where it is acting. This is because the vanadium complex no longer exists in its initial form.

Highly 2,3-selective polymerization of phenylallene and the derivatives by vanadium complexes

Vanadium complex containing bulky ligand were investigated for the allene polymerization. Such complexes exhibited distinguished 2,3-selectivity (>99 %) for phenylallene (PA) polymerization which were proved by the corresponding NMR spectra....

Determination of the naturally occurring vanadium-complex amavadin in Amanita muscaria with HPLC-ICPMS

The determination of the two isomers of amavadin and other V species in Amanita muscaria with HPLC-ICPMS.

Cell Arrest and Apoptosis Induced by the Next Generation of Vanadium Based Drugs: Action Mechanism to Structure Relation and Future Perspectives

Background: Every year we encounter more projects indicating the promising anticancer activity of vanadium molecules against different types of cancer cells. The new generation of metal-based drugs are targeting the energy supplies of the cell through ROS generation leading them to cell arrest and apoptosis. The relatively low toxicity of vanadium metal, the different oxidation states that it can be occurred and in general, the lipophilicity of transition metals, gave attention to vanadium after the exhausted research in platinumbased drugs. Herein, we are reviewing the latest advances in apoptotic activity of vanadium complex molecules and trying to reveal the structure to action relationship. Future perspectives of vanadium anticancer drugs also discussed. Methods: Data were collected from Web of Science, Scopus, Pubmed, through searching of these keywords: “apoptosis”, “anticancer drugs”, “vanadium complexes”, “synthesis” and “cell arrest”. Results: A good amount of vanadium complexes gave promising results over the last years showing that a more careful approach of a ligand design, could give a rise to the next generation of vanadium drugs. Conclusion: The low toxicity of vanadium ion in combination with its V(IV) species selectivity, gives to the vanadium, a head starts against other transition metal complexes.