Search Results (31)

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory loss and limited therapeutic options. Metal-based drugs have emerged as promising alternatives in the search for effective treatments, and vanadium coordination complexes have shown significant potential due to their neuroprotective and anti-aggregant properties. This review explores the advances in the development of vanadium-based metallodrugs for AD, focusing on their ability to modulate amyloid-beta (Aβ) aggregation, oxidative stress, and neuroinflammation. Recent in vitro and in vivo studies highlight the efficacy of oxovanadium (IV) and peroxovanadium (V) complexes in inhibiting Aβ fibril formation and reducing neuronal toxicity. Additionally, the interaction of vanadium complexes with key biological targets, such as peroxisome proliferator-activated receptor gamma (PPARγ) and protein-tyrosine phosphatase 1B (PTP1B), suggests a multifaceted therapeutic approach. While these findings underscore the potential of vanadium compounds as innovative treatments for AD, further research is needed to optimize their bioavailability, selectivity, and safety for clinical applications. Full article

We report the synthesis and characterization of five novel metal complexes. Three of them are vanadium complexes with the general formula [VO(Lⁿ)₂], where Lⁿ are Schiff bases derived from the condensation of 2-carbaldehyde-8-hydroxyquinoline with either 4-(2-aminoethyl)morpholine (L¹), 3-morpholinopropylamine (L²) or 1-(2-aminoethyl)piperidine (L³). The two other metal complexes are [Ni(L¹)₂] and [Fe(L¹)₂]Cl. They were characterized by analytical, spectroscopic (Fourier transform infrared, UV-visible absorption), and mass spectrometric techniques as well as by single-crystal X-ray diffraction (for all [VO(Lⁿ)₂] complexes and [Ni(L¹)₂]). While, in the crystal structure, the V(IV)O complexes show distorted square–pyramidal geometry with the ligands bound as bidentate through quinolate NO donors, the Ni(II) complex shows octahedral geometry with two ligand molecules coordinated through NNO donors. Stability studies in aqueous media revealed that the vanadium complexes are not stable, undergoing oxidation to VO₂(L), which was corroborated by ⁵¹V NMR and MS. This behavior is also observed in organic media, though at a significantly slower rate. The Ni complex exhibited small spectral changes over time in aqueous media. Nonetheless, all compounds show enhanced stability in the presence of bovine serum albumin (BSA). Fluorescence studies carried out for the Ni(II) and Fe(III) complexes indicate reversible binding to albumin. The cytotoxicity of the L¹ metal complexes was assessed on melanoma (B16F10 and A375) and colon cancer (CT-26 and HCT-116) cell lines, with 5-fluorouracil (5-FU) as a reference drug. The V- and Ni complexes showed the lowest IC₅₀ values (<10 μM) in either A375 or HCT-116 cells after 48 h of incubation, while the Fe(III) complex presented minimal antiproliferative effects. The complexes were generally more cytotoxic to human than murine cancer cells. Synergistic in vitro studies with 5-FU revealed antagonism in most cases, except in A375 cells, where an additive effect was observed for the combination with the V-complex. Overall, these compounds show promising potential for cancer treatment, mostly for melanoma. Full article

Since 2020, the attention of the scientific community has been focused on the overwhelming COVID-19 pandemic, the infectious disease caused by the coronavirus that has affected populations worldwide. The alarming number of deaths and the severity of the symptoms have driven studies aimed at combating this disease. One of the key components in the development of this disease is the protein M^Pro, responsible for the replication and transcription of the virus, making it an excellent biological target in research efforts seeking an effective treatment for the disease. Furthermore, studies have shown that vanadium complexes, such as bis(N′,N′-dimethylbiguanide)oxovanadium (IV), VO(metf)₂∙H₂O, exhibit highly promising effects for the treatment of COVID-19. This molecule contains a ligand known as metformin, which also holds a prominent place as a potential agent in the treatment of this disease due to its antiviral properties. Therefore, an investigation into the interactions between these two systems (M^Pro+Vanadium Complex and M^Pro+Metformin) is pertinent given the significance of these two molecules. Thus, computational studies such as molecular docking and classical molecular dynamics are considered advantageous, assisting in this comparative study, as well as providing a deeper understanding of the interactions that occur within each of them. Full article

Lipopolysaccharides (LPS) are bacterial mediators of neuroinflammation that have been detected in close association with pathological protein aggregations of Alzheimer’s disease. LPS induce the release of cytokines by microglia and mediate the upregulation of inducible nitric oxide synthase (iNOS)—a mechanism also associated with amyloidosis. Curcumin is a recognized natural medicine but has extremely low bioavailability. V-Cur, a novel hemocompatible Vanadium(IV)-curcumin complex with higher solubility and bioactivity than curcumin, is studied here. Co-cultures consisting of rat primary neurons and microglia were treated with LPS and/or curcumin or V-Cur. V-Cur disrupted LPS-induced overexpression of amyloid precursor protein (APP) and the in vitro aggregation of human insulin (HI), more effectively than curcumin. Cell stimulation with LPS also increased full-length, inactive, and total iNOS levels, and the inflammation markers IL-1β and TNF-α. Both curcumin and V-Cur alleviated these effects, with V-Cur reducing iNOS levels more than curcumin. Complementary insights into possible bioactivity mechanisms of both curcumin and V-Cur were provided by In silico molecular docking calculations on Aβ_1-42, APP, Aβ fibrils, HI, and iNOS. This study renders curcumin-based compounds a promising anti-inflammatory intervention that may be proven a strong tool in the effort to mitigate neurodegenerative disease pathology and neuroinflammatory conditions. Full article

Diabetes mellitus (DM) complications are a burden to health care systems due to the associated consequences of poor glycemic control and the side effects of insulin therapy. Recently. adjuvant therapies, such as vanadium compounds, have gained attention due to their potential to improve glucose homeostasis in patients with diabetes. In order to determine the anti-diabetic and antioxidant effects of the oxidovanadium(IV) complex (Et₃NH)₂[{VO(OH}₂)(ox)₂(µ–ox)] or Vox2), rats with streptozotocin (STZ)-induced diabetes were treated with 30 and 100 mg/kg of Vox2, orally administered for 12 days. Vox2 at 100 mg/kg in association with insulin caused a 3.4 times decrease in blood glucose in STZ rats (424 mg/dL), reaching concentrations similar to those in the normoglycemic animals (126 mg/dL). Compared to insulin alone, the association with Vox2 caused an additional decrease in blood glucose of 39% and 65% at 30 and 100 mg/kg, respectively, and an increased pancreatic GSH levels 2.5 times. Vox2 alone did not cause gastrointestinal discomfort, diarrhea, and hepatic or renal toxicity and was not associated with changes in blood glucose level, lipid profile, or kidney or liver function. Our results highlight the potential of Vox2 in association with insulin in treating diabetes. Full article

In the text, the synthesis and characteristics of the novel ONS-type vanadium (V) complexes with thioanilide derivatives of amino acids are described. They showed the inhibition of human protein tyrosine phosphatases (PTP1B, LAR, SHP1, and SHP2) in the submicromolar range, as well as the inhibition of non-tyrosine phosphatases (CDC25A and PPA2) similar to bis(maltolato)oxidovanadium(IV) (BMOV). The ONS complexes increased [14C]-deoxy-D-glucose transport into C2C12 myocytes, and one of them, VC070, also enhanced this transport in 3T3-L1 adipocytes. These complexes inhibited gluconeogenesis in hepatocytes HepG2, but none of them decreased lipid accumulation in the non-alcoholic fatty liver disease model using the same cells. Compared to the tested ONO-type vanadium complexes with 5-bromosalicylaldehyde and substituted benzhydrazides as Schiff base ligand components, the ONS complexes revealed stronger inhibition of protein tyrosine phosphatases, but the ONO complexes showed greater activity in the cell models in general. Moreover, the majority of the active complexes from both groups showed better effects than VOSO₄ and BMOV. Complexes from both groups activated AKT and ERK signaling pathways in hepatocytes to a comparable extent. One of the ONO complexes, VC068, showed activity in all of the above models, including also glucose utilizatiand ONO Complexes are Inhibitors ofon in the myocytes and glucose transport in insulin-resistant hepatocytes. The discussion section explicates the results within the wider scope of the knowledge about vanadium complexes. Full article

The reaction of the vanadyl ion (VO²⁺) with imidazole-4-carboxylic acid (Im4COOH), imidazole-2-carboxylic acid (Im2COOH) and methylimidazole-2-carboxylic acid (MeIm2COOH), respectively, in the presence of small bioligands (bL) [oxalate (Ox), lactate (Lact), citrate (Cit) and phosphate (Phos)] and high-molecular-weight (HMW) human serum proteins [albumin (HSA) and transferrin (hTf)] were studied in aqueous solution using potentiometric acid–base titrations. The species distribution diagrams for the high-molecular-mass (HMM) proteins with oxidovanadium(IV) under physiological pH were dominated by VO(HMM)₂, VOL(HMM) for unsubstituted ligands (L⁻ = Im4COO⁻ and Im2COO⁻). However, for the N-substituted MeIm2COOH, the species distribution diagrams under physiological pH were dominated by VOL₂, VO(HMM)₂ and VO₂L₂(HMM). These species were further confirmed by LC-MS, MALDI-TOF-MS and EPR studies. The glucose-stimulated insulin secretion (GSIS) action of the complexes was investigated using INS-1E cells at a 1 µM concentration, which was established through cytotoxicity studies via the MTT assay. The neutral complexes, especially VO(MeIm2COO)₂, showed promising results in the stimulation of insulin secretion than the cationic [VO(MeIm2CH₂OH)₂]²⁺ complex and the vanadium salt. Oxidovanadium(IV) complexes reduced insulin stimulation significantly under normoglycaemic levels but showed positive effects on insulin secretion under hyperglycaemic conditions (33.3 mM glucose media). The islets exposed to oxidovanadium(IV) complexes under hyperglycaemic conditions displayed a significant increase in the stimulatory index with 1.19, 1.75, 1.53, 1.85, 2.20 and 1.29 observed for the positive control (sulfonylurea:gliclazide), VOSO₄, VO(Im4COO)₂, VO(Im2COO)₂, VO(MeIm2COO)₂ and VO(MeIm2CH₂OH)₂²⁺, respectively. This observation showed a potential further effect of vanadium complexes towards type 2 diabetes and has been demonstrated for the first time in this study. Full article

Repurposing drugs by uncovering new indications for approved drugs accelerates the process of establishing new treatments and reduces the high costs of drug discovery and development. Metal complexes with clinically approved drugs allow further opportunities in cancer therapy—many vanadium compounds have previously shown antitumor effects, which makes vanadium a suitable metal to complex with therapeutic drugs, potentially improving their efficacy in cancer treatment. In this review, covering the last 25 years of research in the field, we identified non-oncology-approved drugs suitable as ligands to obtain different vanadium complexes. Metformin-decavanadate, vanadium-bisphosphonates, vanadyl(IV) complexes with non-steroidal anti-inflammatory drugs, and cetirizine and imidazole-based oxidovanadium(IV) complexes, each has a parent drug known to have different medicinal properties and therapeutic indications, and all showed potential as novel anticancer treatments. Nevertheless, the precise mechanisms of action for these vanadium compounds against cancer are still not fully understood. Full article

Early phase diagnosis of human diseases has still been a challenge in the medicinal field, and one of the efficient non-invasive techniques that is vastly used for this purpose is magnetic resonance imaging (MRI). MRI is able to detect a wide range of diseases and conditions, including nervous system disorders and cancer, and uses the principles of NMR relaxation to generate detailed internal images of the body. For such investigation, different metal complexes have been studied as potential MRI contrast agents. With this in mind, this work aims to investigate two systems containing the vanadium complexes [VO(metf)₂]·H₂O (VC1) and [VO(bpy)₂Cl]⁺ (VC2), being metformin and bipyridine ligands of the respective complexes, with the biological targets AMPK and ULK1. These biomolecules are involved in the progression of Alzheimer’s disease and triple-negative breast cancer, respectively, and may act as promising spectroscopic probes for detection of these diseases. To initially evaluate the behavior of the studied ligands within the aforementioned protein active sites and aqueous environment, four classical molecular dynamics (MD) simulations including VC1 + H₂O (1), VC2 + H₂O (2), VC1 + AMPK + H₂O (3), and VC2 + ULK1 + H₂O (4) were performed. From this, it was obtained that for both systems containing VCs and water only, the theoretical calculations implied a higher efficiency when compared with DOTAREM, a famous commercially available contrast agent for MRI. This result is maintained when evaluating the system containing VC1 + AMPK + H₂O. Nevertheless, for the system VC2 + ULK1 + H₂O, there was observed a decrease in the vanadium complex efficiency due to the presence of a relevant steric hindrance. Despite that, due to the nature of the interaction between VC2 and ULK1, and the nature of its ligands, the study gives an insight that some modifications on VC2 structure might improve its efficiency as an MRI probe. Full article

In Earth’s regions accessible for living organisms (Earth’s crust, crude oil, water sanctuaries and lower atmosphere), vanadium is present in the oxidation states +III and—essentially—+IV (cationic) and +V (cationic and anionic), with the redox interchange and biochemical recycling often monitored by bacteria. Organisms having available vanadium-containing (bio)molecules with essential functions for life include marine brown algae (haloperoxidases), ascidians and fan worms, as well as terrestrial organisms, viz., nitrogen-fixing bacteria (associated with the roots of legumes), and the fly agaric mushroom. The hypohalite generated by the algal haloperoxidases in turn is involved in the emission of bromoform into the atmosphere. Nitrogen fixation (N₂ ε NH₄⁺) is a process of immanent importance for life on our planet. Other bacterial issues include the reduction of vanadate to VO²⁺. Medicinal applications of vanadium coordination compounds are directed towards the treatment of diabetes mellitus (vanadium complexes with hypoglycemic activity) and cancer—although boundaries are set due to side effects such as oxidative damage elicited by vanadium-induced hyperoxide formation. Physiological actions of vanadium are often invoked due to the structural and physiological similarity between vanadate and phosphate. An additional field of medicinal applications addresses the treatment of cancer, such as leukaemia, malignant melanoma and bone cancer. Full article

Two new monobasic tridentate O⁀N⁀N donor ligands, HL₁ (I) and HL₂ (II) have been obtained in two steps by reacting phenylhydrazine and salicylaldehyde or 3,5-di-tert-butylsalicylaldehyde and then reacting the resulting compounds with 2-chloromethylbenzimidazole in the presence of triethylamine. The reaction of [V^IVO(acac)₂] with these ligands in a 1:1 molar ratio in dry methanol led to the formation of homogeneous oxidovanadium(IV) complexes [V^IVO(acac)L₁] (1) and [V^IVO(acac)L₂] (2). Immobilization of these complexes on chloromethylated polystyrene (PS-Cl) cross-linked with divinyl benzene resulted in corresponding polymer-supported heterogeneous complexes PS-[V^IVO(acac)L₁] (3) and PS-[V^IVO(acac)L₂] (4). Ligands (I and II), homogeneous complexes (1 and 2) and heterogeneous complexes (3 and 4) have been characterized using elemental analysis and various spectroscopic techniques. A single crystal X-ray diffraction study of I and 1 further confirms their structures. The oxidation state IV of vanadium in these complexes was assured by recording their EPR spectra while heterogeneous complexes were further characterized using field emission-scanning electron microscopy (FE-SEM) combined with energy dispersive X-ray analysis (EDS) and atomic force microscopy (AFM). All vanadium complexes have been explored for their catalytic potential to one-pot-three-component reactions (reagents: benzil, ammonium acetate and various aromatic aldehydes) for the efficient synthesis of 2,4,5-triphenyl-1H-imidazole derivatives (nine examples). Various reaction conditions have been optimized to obtain a maximum yield (up to 96%) of catalytic products. It has been found that heterogeneous complexes show excellent catalytic activity and are recyclable up to five catalytic cycles. Full article

The search for less expensive and viable products is always one of the challenges for research development. Commonly, the synthesis of coordination compounds involves expensive ligands, through expensive and low-yield routes, in addition to generating toxic and unusable residues. In this work, the organic ligand used is derived from the resin of a reforestation tree, Pinus elliottii var. elliottii. The synthesis method used Pinus resin and an aqueous solution of vanadium(III) chloride at a temperature of 80 °C. The procedure does not involve organic solvents and does not generate toxic residues, thus imparting the complex formation reaction a green chemistry character. The synthesis resulted in an unprecedented oxovanadium(IV)-bis(abietate) complex, which was characterized by mass spectrometry (MS), chemical analysis (CHN), vibrational (FTIR) and electronic spectra (VISIBLE), X-ray diffraction (XRD), and thermal analysis (TG/DTA). Colorimetric studies were performed according to the CIELAB color space. The structural formula found, consisted of a complex containing two abietate ligands, [VO(C₂₀H₂₉O₂)₂]. The VO(IV)-bis(abietate) complex was applied against microorganisms and showed promising results in antibacterial and antifungal activity. The best result of inhibitory action was against the strains of Gram-positive bacteria S. aureus and L. monocytogenes, with minimum inhibitory concentration (MIC) values of 62.5 and 125 μmol L⁻¹, respectively. For Gram-negative strains the results were 500 μmol L⁻¹ for E. coli; and 1000 μmol L⁻¹ for Salmonella enterica Typhimurium. Antifungal activity was performed against Candida albicans, where the MIC was 15.62 μmol L⁻¹, and for C. tropicalis it was 62.5 μmol L⁻¹. According to the MFC analysis, the complex presented, in addition to the fungistatic action, a fungicidal action, as there was no growth of fungi on the plates tested. The results found for the tests demonstrate that the VO(IV)-bis(abietate) complex has great potential as an antimicrobial and mainly antifungal agent. In this way, the pigmented ink with antimicrobial activity could be used in environments with a potential risk of contamination, preventing the spread of microorganisms harmful to health. Full article

The technology of simultaneously recovering V and Ti from vanadium slag via ammonium salt roasting has proven to be an efficient route. However, due to the phase stability and complex chemical composition of vanadium slag, intermediate materials containing Fe, V, Ti and Mn are difficult to be characterized critically. This work aims to investigate the decomposition and transformation of vanadium slag during ammonium salt roasting, using a combination of FT-IR, XRD, XPS and SEM techniques. It was found that the lattice structure of Fe-contained spinel would be transformed from FeV₂O₄ to Fe²⁺V_nFe_2−nO₄ (0 < n < 2) during directly roasting in the air. However, there is no obvious change for Ti-contained and Mn-contained spinel. Using NH₄HSO₄ (ABS) as an additive and roasting the slag in the N₂ atmosphere, those spinels would be decomposed into various sulfate salts. Meanwhile, when the slag was roasted with NH₄HSO₄ in the air, a part of Fe(II) in (NH₄)₂Fe(SO₄)₂ would be transferred into Fe(III), but V(III), Ti(IV) and Mn(II) from those salts would remain the same valance state. Ultimately, about 88% V and 81% Ti were recovered, when vanadium slag was roasted at 663.15 K with a 1:5 ratio of slag-to-NH₄HSO₄ and followed by 8 vol.% H₂SO₄ leaching. Full article

One of the main goals of recent bioinorganic chemistry studies has been to design and synthesize novel substances to treat human diseases. The promising compounds are metal-based and metal ion binding components such as vanadium-based compounds. The potential anticancer action of vanadium-based compounds is one of area of investigation in this field. In this study, we present five oxovanadium(IV) and dioxovanadium(V) complexes as potential PTP1B inhibitors with anticancer activity against the MCF-7 breast cancer cell line, the triple negative MDA-MB-231 breast cancer cell line, and the human keratinocyte HaCaT cell line. We observed that all tested compounds were effective inhibitors of PTP1B, which correlates with anticancer activity. [VO(dipic)(dmbipy)]·2 H₂O (Compound 4) and [VOO(dipic)](2-phepyH)·H₂O (Compound 5) possessed the greatest inhibitory effect, with IC₅₀ 185.4 ± 9.8 and 167.2 ± 8.0 nM, respectively. To obtain a better understanding of the relationship between the structure of the examined compounds and their activity, we performed a computer simulation of their binding inside the active site of PTP1B. We observed a stronger binding of complexes containing dipicolinic acid with PTP1B. Based on our simulations, we suggested that the studied complexes exert their activity by stabilizing the WPD-loop in an open position and limiting access to the P-loop. Full article

Vanadium compounds have been set in various fields as anticancer, anti-diabetic, anti-parasitic, anti-viral, and anti-bacterial agents. This study reports the synthesis and structural characterization of oxidovanadium(IV)-based imidazole drug complexes by the elemental analyzer, molar conductance, magnetic moment, spectroscopic techniques, as well as thermal analysis. The obtained geometries were studied theoretically using density functional theory (DFT) under the B3LYP level. The DNA-binding nature of the ligands and their synthesized complexes has been studied by the electronic absorption titrations method. The biological studies were carried with in-vivo assays and the molecular docking method. The EPR spectra asserted the geometry around the vanadium center to be a square pyramid for metal complexes. The geometries have been confirmed using DFT under the B3LYP level. Moreover, the quantum parameters proposed promising bioactivity of the oxidovanadium(IV) complexes. The results of the DNA-binding revealed that the investigated complexes bind to DNA via non-covalent mode, and the intrinsic binding constant (K_b) value for the [VO(SO₄)(MNZ)₂] H₂O complex was promising, which was 2.0 × 10⁶ M⁻¹. Additionally, the cytotoxic activity of the synthesized complexes exhibited good inhibition toward both hepatocellular carcinoma (HepG-2) and human breast cancer (HCF-7) cell lines. The results of molecular docking displayed good correlations with experimental cytotoxicity findings. Therefore, these findings suggest that our synthesized complexes can be introduced as effective anticancer agents. Full article