Recent Advances and Future Approaches in Preventive and Therapeutic Effects of Vanadium Complexes

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: 31 October 2024 | Viewed by 8327

Special Issue Editors


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Guest Editor
Department of Cytobiology, Pharmaceutical Faculty, Jagiellonian University Medical College, Medyczna 9, 30-688 Krakow, Poland
Interests: anticancer activity; plant phenolics; leukemia; apoptosis; cell cycle; DNA repair; flow cytometry

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Guest Editor
Department of Medical Diagnostics, Medical College, Jagiellonian University, 31-688 Kraków, Poland
Interests: metabolic activity of the brain's diseases like neuropsychiatric, stroke; redox signaling, tooth decay, biostatistics, biomaterials; composites; drug delivery systems
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Special Issue Information

Dear Colleagues,

Vanadium is a trace element of interest due to the therapeutic properties of its organic and inorganic complexes. Vanadium can have a Lewis acid character and occurs in a variety of oxidative states, the most common of which are the tetravalent and pentavalent forms. Its high reactivity is used to form various inorganic and organic compounds. Because transition metal compounds can reduce toxicity and improve bioavailability of free organic ligands and the elements themselves, they are being investigated for applications in the treatment of many diseases. Vanadium is characterized by nephrotoxicity, as demonstrated in in vivo studies. Therefore, metallodrugs with less toxicity than the element itself are sought in vanadium complexes, especially organic ones.

Vanadium complexes may have potential therapeutic applications in the treatment of type 2 diabetes, cancer or infection diseases. Vanadium's activity mimics that of phosphates, so it can modify the action of kinases and phosphatases, which explains its antidiabetic, anticancer, cardioprotective, and antimicrobial effects.

This Special Issue aims to present research on new vanadium complexes with protective effects against metabolic disorders, with antidiabetic or antiobesity activity. Work on other potential therapeutic applications of vanadium compounds, such as anticancer, antimicrobial, cardioprotective, and neuroprotective properties not yet demonstrated in research, will also be well received.

Dr. Monika A. Papież
Dr. Wirginia Krzyściak
Guest Editors

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Keywords

  • vanadium compounds
  • antidiabetic, insulinomimetic
  • antiobesity
  • anticancer
  • antimicrobial
  • cardioprotective
  • neuroprotective

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Published Papers (5 papers)

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Research

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17 pages, 2179 KiB  
Article
Dexamethasone-Induced Insulin Resistance Attenuation by Oral Sulfur–Oxidovanadium(IV) Complex Treatment in Mice
by Eucilene K. Batista, Lidiane M. A. de Lima, Dayane A. Gomes, Debbie C. Crans, Wagner E. Silva, Mônica F. Belian and Eduardo C. Lira
Pharmaceuticals 2024, 17(6), 760; https://doi.org/10.3390/ph17060760 - 10 Jun 2024
Viewed by 894
Abstract
Vanadium compounds are known to exert insulin-enhancing activity, normalize elevated blood glucose levels in diabetic subjects, and show significant activity in models of insulin resistance (IR). Faced with insulin resistance, the present work investigates the antidiabetic performance of a known oxidovanadium(IV)-based coordination compound—[V [...] Read more.
Vanadium compounds are known to exert insulin-enhancing activity, normalize elevated blood glucose levels in diabetic subjects, and show significant activity in models of insulin resistance (IR). Faced with insulin resistance, the present work investigates the antidiabetic performance of a known oxidovanadium(IV)-based coordination compound—[VIVO(octd)]—and effects associated with glucocorticoid-induced insulin resistance in mice. The effects of [VIVO(octd)] were evaluated in a female Swiss mice model of insulin resistance induced by seven days of dexamethasone treatment in comparison with groups receiving metformin treatment. Biological assays such as hematological, TyG index, hepatic lipids, glycogen, oxidative stress in the liver, and oral glucose tolerance tests were evaluated. [VIVO(octd)] was characterized with 51V NMR, infrared spectroscopy (FTIR), electron paramagnetic resonance (EPR), electronic absorption spectroscopy, and mass spectrometry (ESI–FT–MS). The [VIVO(octd)] oral treatment (50 mg/kg) had an antioxidant effect, reducing 50% of fast blood glucose (p < 0.05) and 25% of the TyG index, which is used to estimate insulin resistance (p < 0.05), compared with the non-treated group. The oxidovanadium–sulfur compound is a promising antihyperglycemic therapeutic, including in cases aggravated by insulin resistance induced by glucocorticoid treatment. Full article
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19 pages, 1562 KiB  
Article
A Non-Toxic Binuclear Vanadium(IV) Complex as Insulin Adjuvant Improves the Glycemic Control in Streptozotocin-Induced Diabetic Rats
by Mateus S. Lopes, Gabriel B. Baptistella, Giovana G. Nunes, Matheus V. Ferreira, Joice Maria Cunha, Kauê Marcel de Oliveira, Alexandra Acco, Maria Luiza C. Lopes, Alexessander Couto Alves, Glaucio Valdameri, Vivian R. Moure, Geraldo Picheth, Graciele C. M. Manica and Fabiane G. M. Rego
Pharmaceuticals 2024, 17(4), 486; https://doi.org/10.3390/ph17040486 - 11 Apr 2024
Viewed by 1453
Abstract
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 [...] Read more.
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
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35 pages, 6451 KiB  
Article
Vanadium Complexes with Thioanilide Derivatives of Amino Acids: Inhibition of Human Phosphatases and Specificity in Various Cell Models of Metabolic Disturbances
by Grzegorz Kazek, Monika Głuch-Lutwin, Barbara Mordyl, Elżbieta Menaszek, Monika Kubacka, Anna Jurowska, Dariusz Cież, Bartosz Trzewik, Janusz Szklarzewicz and Monika A. Papież
Pharmaceuticals 2024, 17(2), 229; https://doi.org/10.3390/ph17020229 - 9 Feb 2024
Viewed by 1668
Abstract
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 [...] Read more.
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
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14 pages, 3305 KiB  
Article
MD Simulations to Calculate NMR Relaxation Parameters of Vanadium(IV) Complexes: A Promising Diagnostic Tool for Cancer and Alzheimer’s Disease
by Rodrigo Mancini Santos, Camila Assis Tavares, Taináh Martins Resende Santos, Hassan Rasouli and Teodorico Castro Ramalho
Pharmaceuticals 2023, 16(12), 1653; https://doi.org/10.3390/ph16121653 - 27 Nov 2023
Viewed by 1757
Abstract
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 [...] Read more.
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
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Review

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14 pages, 1752 KiB  
Review
Repurposing Therapeutic Drugs Complexed to Vanadium in Cancer
by Ana Luísa De Sousa-Coelho, Gil Fraqueza and Manuel Aureliano
Pharmaceuticals 2024, 17(1), 12; https://doi.org/10.3390/ph17010012 - 21 Dec 2023
Cited by 8 | Viewed by 1720
Abstract
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 [...] Read more.
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
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