Bimetallic bis-Aroyldihydrazone-Isatin Complexes of High O=V(IV) and Low Cu(II) Valent Ions as Effective Biological Reagents for Antimicrobial and Anticancer Assays.

Due to the versatile bioreactivity of aroyldihydrazone complexes as cost-effective alternatives with different transition metals, two novel bimetallic homo-complexes (VOLph and CuLph) were prepared via the coordination of a terephthalic dihydrazone diisatin ligand (H2Lph) with VO2+ and Cu2+ ions, respectively. The structure elucidation was confirmed by alternative spectral methods. Biologically, the H2Lph ligand and its MLph complexes (M2+ = VO2+ or Cu2+) were investigated as antimicrobial and anticancer agents. Their biochemical activities towards ctDNA (calf thymus DNA) were estimated using measurable titration viscometrically and spectrophotometrically, as well as the gel electrophoresis technique. The growth inhibition of both VOLph and CuLph complexes against microbial and cancer cells was measured, and the inhibition action, MIC, and IC50 were compared to the inhibition action of the free H2Lph ligand. Both VOLph and CuLph showed remarkable interactive binding with ctDNA compared to the free ligand H2Lph, based on Kb = 16.31, 16.04 and 12.41 × 107 mol-1 dm3 and ΔGb≠ = 47.11, -46.89, and -44.05 kJ mol-1 for VOLph, CuLph, and H2Lph, respectively, due to the central metal ion (VIVO and CuII ions). VOLph (with a higher oxidation state of the V4+ ion and oxo-ligand) exhibited enhanced interaction with the ctDNA molecule compared to CuLph, demonstrating the role and type of the central metal ion within the performed electronegative and electrophilic characters.

Synthesis, In Vitro, and Computational Studies of PTP1B Phosphatase Inhibitors Based on Oxovanadium(IV) and Dioxovanadium(V) Complexes.

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.

A Series of Green Oxovanadium(IV) Precatalysts with O, N and S Donor Ligands in a Sustainable Olefins Oligomerization Process.

Designing catalyst systems based on transition metal ions and activators using the principles of green chemistry is a fundamental research goal of scientists due to the reduction of poisonous solvents, metal salts and organic ligands released into the environment. Urgent measures to reduce climate change are in line with the goals of sustainable development and the new restrictive laws ordained by the European Union. In this report, we attempted to use known oxovanadium(IV) green complex compounds with O, N and S donor ligands, i.e., [VO(TDA)phen] • 1.5 H2O (TDA = thiodiacetate), (phen = 1,10-phenanthroline), oxovanadium(IV) microclusters with 2-phenylpyridine (oxovanadium(IV) cage), [VOO(dipic)(2-phepyH)] • H2O (dipic = pyridine-2,6-dicarboxylate anion), (2-phepyH = 2-phenylpyridine), [VO(dipic)(dmbipy)] • 2H2O (dmbipy = 4,4'-dimethoxy-2,2'-dipyridyl) and [VO(ODA)(bipy)] • 2 H2O (ODA = oxydiacetate), (bipy = 2,2'-bipyridine), as precatalysts in oligomerization reactions of 3-buten-2-ol, 2-propen-1-ol, 2-chloro-2-propen-1-ol and 2,3-dibromo-2-propen-1-ol. The precatalysts, in most cases, turned out to be highly active because the catalytic activity exceeded 1000 g mmol-1·h-1. In addition, the oligomers were characterized by Fourier-transform infrared spectroscopy (FTIR), matrix-assisted laser desorption/ionization (MALDI-TOF-MS), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) techniques.

Relationship between Antioxidant Activity and Ligand Basicity in the Dipicolinate Series of Oxovanadium(IV) and Dioxovanadium(V) Complexes.

Oxidative stress plays an important role in the pathogenesis of many serious diseases, including cancer, atherosclerosis, coronary artery disease, Parkinson's disease, Alzheimer's disease, stroke and myocardial infarction. In the body's natural biochemical processes, harmful free radicals are formed, which can be removed with the help of appropriate enzymes, a balanced diet or the supply of synthetic antioxidant substances such as flavonoids, vitamins or anthocyanins to the body. Due to the growing demand for antioxidant substances, new complex compounds of transition metal ions with potential antioxidant activity are constantly being sought. In this study, four oxovanadium(IV) and dioxovanadium(V) dipicolinate (dipic) complexes with 1,10-phenanthroline (phen), 2,2'-bipyridyl (bipy) and the protonated form of 2-phenylpyridine (2-phephyH): (1) [VO(dipic)(H2O)2]·2 H2O, (2) [VO(dipic)(phen)]·3 H2O, (3) [VO(dipic)(bipy)]·H2O and (4) [VOO(dipic)](2-phepyH)·H2O were synthesized including one new complex, so far unknown and not described in the literature, i.e., [VOO(dipic)](2-phepyH)·H2O. The oxovanadium(IV) dipicolinate complexes with 1,10-phenanthroline and 2,2'-bipyridyl have been characterized by several physicochemical methods: NMR, MALDI-TOF-MS, IR, but new complex [VOO(dipic)](2-phepyH)·H2O has been examined by XRD to confirm its structure. The antioxidant activities of four complexes have been examined by the nitrotetrazolium blue (NBT) method towards superoxide anion. All complexes exhibit high reactivity with superoxide anion and [VOO(dipic)](2-phepyH)·H2O has higher antioxidant activity than L-ascorbic acid. Our studies confirmed that high basicity of the auxiliary ligand increases the reactivity of the complex with the superoxide radical.

Glycoprotein levels and oxidative lung injury in experimental diabetes: effect of oxovanadium(IV) complex based on thiosemicarbazone.

Diabetes mellitus (DM) is chronic and metabolic disorder, which is mainly attributed by hyperglycemia. Vanadium salts and their oxo-complexes have been shown to possess insulin-mimetic and anti-diabetic activities in animal models and diabetic patients. The main goal of this study was to investigate the protective effect of oxovanadium(IV) complex based on thiosemicarbazone (VOL) [L: (N(1)-2,4-dihydroxybenzylidene-N-(4)-2-hydroxybenzylidene-S-methyl-isothiosemicarbazidato-oxovanadium(IV)] on glycoprotein components levels and oxidative lung injury of streptozotocin (STZ)-induced diabetic rats. Male Swiss albino rats were separated into four groups. Group I (n = 5): Control (normal) animals, Group II (n = 5): Control animals administered with VOL, Group III (n = 6): STZ-induced diabetic animals, and Group IV (n = 5): STZ-induced diabetic rats treated with VOL. VOL was given to the experimental animals by gavage at a dose of 0.2 mM/kg body weight every day for 12 days. Diabetes was induced by single intraperitoneal injection of STZ (65 mg/kg body weight). On the 12th day, lung tissue samples were taken. Glycoprotein components, advanced oxidation protein products, protein carbonyl, hydroxyproline levels, and prolidase, arginase, xanthine oxidase, catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase and adenosine deaminase activities significantly increased whereas aryl esterase, paraoxonase-1, carbonic anhydrase, Na+/K+-ATPase activities remarkably decreased in lung tissue of diabetic rats. Treatment with VOL reversed these effects showing a beneficial effect. The present study shows that VOL has a protective effect against diabetes-induced lung damage as well as on abnormal glycoprotein component levels.

Oxovanadium(IV) and Nickel(II) complexes obtained from 2,2'-dihydroxybenzophenone-S-methyl-thiosemicarbazone: Synthesis, characterization, electrochemistry, and antioxidant capability.

2,2'-Dihydroxybenzophenone-S-methyl-thiosemicarbazone and 3-methoxy-salicylaldehyde were reacted in the presence of oxovanadium(IV) or nickel(II) ions to yield the N2O2-type-chelate complex. The synthesized complexes were characterized by employing elemental analysis, electronic and infrared spectra, 1H NMR spectra, magnetic measurements, and thermogravimetric analyses. The expected structures of oxovanadium(IV) and nickel(II) complexes were confirmed by using the single-crystal X-ray diffraction method. The presence of π-π stacked dimeric structures provided stronger crystalline formations. The optimized geometries and vibrational frequencies of the compounds were obtained using the DFT/ωB97XD method with the 6-31G (d,p) basis set and compared with the experimental data. The electrochemical characterization of the oxovanadium(IV) and nickel(II) complexes were carried out by using the cyclic voltammetry (CV) method. The oxovanadium(IV) complex gives a ligand-centered oxidation and a metal-centered one electron reduction and oxidation peaks corresponding to the VIV/IIIO and VIV/VO, respectively. The nickel(II) complex gives a ligand-centered oxidation and metal-centered (NiII/I) reduction peaks in a dimethyl sulfoxide (DMSO) solution. The redox potentials were calculated in terms of Gibbs free energy change of the redox reaction at the theory level of M06-L/LANL2DZ/PCM. In addition, the energy gap, HOMO and LUMO distributions were calculated. The total antioxidant capacities of the compounds were determined by using cupric reducing antioxidant capacity (CUPRAC) method, in which the oxovanadium(IV) complex was found to be powerful as an antioxidant agent.

Vanadium: History, chemistry, interactions with α-amino acids and potential therapeutic applications.

In the last 30 years, since the discovery that vanadium is a cofactor found in certain enzymes of tunicates and possibly in mammals, different vanadium-based drugs have been developed targeting to treat different pathologies. So far, the in vitro studies of the insulin mimetic, antitumor and antiparasitic activity of certain compounds of vanadium have resulted in a great boom of its inorganic and bioinorganic chemistry. Chemical speciation studies of vanadium with amino acids under controlled conditions or, even in blood plasma, are essential for the understanding of the biotransformation of e.g. vanadium antidiabetic complexes at the physiological level, providing clues of their mechanism of action. The present article carries out a bibliographical research emphaticizing the chemical speciation of the vanadium with different amino acids and reviewing also some other important aspects such as its chemistry and therapeutical applications of several vanadium complexes.

Oxovanadium(IV) complexes with Knoevenagel Schiff base condensate as impending chemotherapeutic agents: Synthesis, characterization, biological screening and anti-proliferative assay.

Two novel oxovanadium(IV) complexes [VOL1]SO4(1) and [VOL2]SO4(2) containing Knoevenagel condensate Schiff base ligand (L1/L2) have been synthesized and characterized by physical, spectral and analytical methods. These complexes are reported as ionic in nature on the basis of elemental composition and molar conductance, and possess square pyramidal geometry around the central metal ions. The binding interactions of (1) and (2) with calf thymus DNA (CT DNA) were explored by absorption spectrophotometric titration, cyclic voltammetry data and viscosity measurements. The calculated intrinsic binding constant values (Kb) for (1) and (2) obtained from UV-Vis absorption studies are 0.4×105 and 5.6×105 (M-1) respectively. These experimental results indicate that (1) and (2) are intercalative binders and avid binder to CT DNA with different affinities. These complexes exhibit significant oxidative cleavage of supercoiled plasmid (pUC18) DNA in the presence of activators. In particular, the in vitro antimicrobial efficacy of oxovanadium(IV) complexes reveal that they are more active than free ligands. Besides, the in vitro cytotoxic effect of the titled complexes were examined on a bundle of human tumor cell lines such as MCF-7 and HeLa cancerous cell lines by the MTT method. Interestingly, complex (2) exhibits more potent cytotoxic activity than the other complex and standard drug (cisplatin). The mode of cell death was assessed by Hoechst 33258 staining morphological studies.

Biologically active oxovanadium(IV) Schiff base metal complex: antibacterial, antioxidant, biomolecular interaction and molecular docking studies.

The oxovanadium(IV) Schiff base metal complex (ISNPV) have been synthesized as well as characterized by using micro analytical and traditional spectroscopic techniques. The spectral findings were utilized to validate the formation of ISNPV with structure exhibited square pyramidal geometry. The in vitro antibacterial activities of ISNPV were investigated to five different bacterial stains such as S. aureus, S. epidermidis, B. cereus, B. amyloliquefaciens and B. subtilis. The obtained result have suggested that the ISNPV has highest antibacterial activity against S. aureus than the other bacterial stains. The in vitro antioxidant activity like DPPH free radical scavenging assay method was studied by ISNPV in DMSO medium. Because it scavenges all free radicals, the ISNPV possesses higher antioxidant activity than the free ligand. UV-visible absorption and emission spectral techniques were used to investigate the binding of CT-DNA to the ISNPV. Both the spectral data indicate that the ISNPV binds the double helix structure of CT-DNA via an intercalation mode. Additionally, investigate the interactions of ISNPV with the protein molecules like BSA/HAS has been investigated using absorption and emission techniques. The absorption intensity of metal complex increases as well as the emission intensity of protein molecules ability decreases due to the binding nature of ISNPV with BSA/HSA protein molecules. The binding nature of ISNPV with bio molecules such as CT-DNA, BSA and HSA was also validated using molecular docking approach.

Triazole based Schiff bases and their oxovanadium(IV) complexes: Synthesis, characterization, antibacterial assay, and computational assessments.

The synthesis and characterization of two new Schiff base ligands containing 1,2,4-triazole moieties and their oxovanadium(IV) complexes have been reported. The ligands and their complexes were studied by ultraviolet-visible (UV-Vis), Fourier transform infrared (FTIR), proton nuclear magnetic resonance (1H NMR), electron paramagnetic resonance (EPR), X-ray diffraction (XRD), conductivity measurement, cyclic voltammetry (CV), and elemental analyses. The molar conductance of oxovanadium(IV) complexes were found to be relatively low, depicting their non-electrolytic nature. The XRD patterns reveal the size of particles to be 47.53 nm and 26.28 nm for the two complexes in the monoclinic crystal system. The molecular structures, geometrical parameters, chemical reactivity, stability, and frontier molecular orbital pictures were determined by density functional theory (DFT) calculations. The theoretical vibrational frequencies and EPR g-factors (1.98) were found to correlate well with the experimental values. A distorted square pyramidal geometry with C2 symmetry of the complexes has been proposed from experimental and theoretical results in a synergistic manner. The antimicrobial sensitivity of the ligands and their metal complexes assayed in vitro against four bacterial pathogens viz. Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Salmonella Typhi showed that the oxovanadium(IV) complexes are slightly stronger antibacterial agents than their corresponding Schiff base precursors. The binding affinities obtained from the molecular docking calculations with the receptor proteins of bacterial strains (2EUG, 3UWZ, 4GVF, and 4JVD) showed that the Schiff bases and their oxovanadium(IV) complexes have considerable capacity inferring activeness for effective inhibition. The molecular dynamics simulation of a protein-ligand (4JVD-HL2) complex with the best binding affinity of -12.8 kcal/mol for 100 ns showed acceptable stability of the docked pose and binding free energy of -15.17 ± 2.29 kcal/mol from molecular mechanics-generalized Born surface area (MM-GBSA) calculations indicated spontaneity of the reaction. The outcome of the research shows the complementary role of computational methods in material characterization and provides an interesting avenue to pursue for exploring new triazole based Schiff's bases and its vanadium compounds for better properties.

Encapsulated Oxovanadium(IV) and Dioxovanadium(V) Complexes into Solid Lipid Nanoparticles Increase Cytotoxicity Against MDA-MB-231 Cell Line.

Introduction: Solid lipid nanoparticles (SLN) have been considered lately as promising drug delivery system in treatment of many human diseases including cancers. We previously studied potential drug compounds that were effective inhibitors of PTP1B phosphatase - possible target for breast cancer treatment. Based on our studies, two complexes were selected for encapsulation into the SLNs, the compound 1 ([VO(dipic)(dmbipy)] · 2 H2O) and compound 2 ([VOO(dipic)](2-phepyH) · H2O). Here, we investigate the effect of encapsulation of those compounds on cell cytotoxicity against MDA-MB-231 breast cancer cell line. The study also included the stability evaluation of the obtained nanocarriers with incorporated active substances and characterization of their lipid matrix. Moreover, the cell cytotoxicity studies against the MDA-MB-231 breast cancer cell line in comparison and in combination with vincristine have been performed. Wound healing assay was carried out to observe cell migration rate. Methods: The properties of the SLNs such as particle size, zeta potential (ZP), and polydispersity index (PDI) were investigated. The morphology of SLNs was observed by scanning electron microscopy (SEM), while the crystallinity of the lipid particles was analyzed by differential scanning calorimetry (DSC) and X-ray diffraction (XRD). The cell cytotoxicity of complexes and their encapsulated forms was carried out against MDA-MB-231 breast cancer cell line using standard MTT protocols. The wound healing assay was performed using live imaging microscopy. Results: SLNs with a mean size of 160 ± 25 nm, a ZP of -34.00 ± 0.5, and a polydispersity index of 30 ± 5% were obtained. Encapsulated forms of compounds showed significantly higher cytotoxicity also in co-incubation with vincristine. Moreover, our research shows that the best compound was complex 2 encapsulated into lipid nanoparticles. Conclusion: We observed that encapsulation of studied complexes into SLNs increases their cell cytotoxicity against MDA-MB-231 cell line and enhanced the effect of vincristine.

Dipicolinate Complexes of Oxovanadium(IV) and Dioxovanadium(V) with 2-Phenylpyridine and 4,4'-Dimethoxy-2,2'-bipyridyl as New Precatalysts for Olefin Oligomerization.

Polyolefins are used in everyday life, including in the production of many types of plastic. In addition, polyolefins account for over 50% of the polymers produced in the world. After conducting the oligomerization reactions of 2-propen-1-ol, 2-chloro-2-propen-1-ol, and norborene, polyolefins are obtained. In this report, two complexes of oxovanadium(IV) and dioxovanadium(V) with dipicolinate, 2-phenylyridine, and 4,4'-dimethoxy-2,2'-bipyridyl as precatalysts for 2-propen-1-ol, 2-chloro-2-propen-1-ol, and norborene oligomerizations are prepared. We present for the first time the new dipicolinate complex compound of oxovanadium(IV) with 4,4'-dimetoxy-2,2'-bipyridyl. Both complexes were tested for catalytic activity in the oligomerization reactions of 2-propen-1-ol, 2-chloro-2-propen-1-ol, and norbornene. Both synthesized complexes showed high catalytic activity in these oligomerization reactions, except for the oligomerization of norbornene.

Preparation of Allyl Alcohol Oligomers Using Dipicolinate Oxovanadium(IV) Coordination Compound.

Currently, new precatalysts for olefin oligomerization are being sought in the group of vanadium(IV) complexes. Thus, the aim of our research was to examine the catalytic activity of the oxovanadium(IV) dipicolinate complex [VO(dipic)(H2O)2] 2 H2O (dipic = pyridine-2,6-dicarboxylate anion) in 2-propen-1-ol oligomerization as well as to characterize oligomerization products using matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF-MS), infrared spectroscopy (IR) and nuclear magnetic resonance (NMR). The oligomerization process took place at room temperature, under atmospheric pressure and under nitrogen atmosphere to prevent oxidation of the activator MMAO-12-the modified methylaluminoxane (7 wt.%) aluminum in toluene. The last point was to determine the catalytic activity of the complex in the oligomerization reaction of 2-propen-1-ol. The aspect that enriches this work is the proposed mechanism of oligomerization of allyl alcohol based on the literature.

Combination of bis (α-furancarboxylato) oxovanadium (IV) and metformin improves hepatic steatosis through down-regulating inflammatory pathways in high-fat diet-induced obese C57BL/6J mice.

The effects of the combination of bis (α-furancarboxylato) oxovanadium (IV) (BFOV) and metformin (Met) on hepatic steatosis were investigated in high-fat diet-induced obese C57BL/6J mice (HFC57 mice) for 6 weeks. Oral glucose tolerance test was performed to evaluate glucose metabolism. Moreover, blood and hepatic biochemical and histological indices were detected. Besides, Affymetrix-GeneChip analysis and Western blot of the liver were performed. Comparing to the monotherapy group, BFOV + Met showed more effective improvement in glucose metabolism, which decreased the fasting blood glucose, insulin levels and improved insulin sensitivity in HFC57 mice. BFOV + Met significantly decreased serum ALT and AST activities and reduced hepatic triglyceride content and iNOS activities, accompanied by ameliorating intrahepatic fat accumulation and hepatocellular vacuolation. Enhanced hepatic insulin signalling transduction and attenuated inflammation pathway were identified as the major pathways in the BFOV + Met group. BFOV + Met significantly down-regulated the protein expression levels of MMPs, NF-κB, iNOS and up-regulated phosphorylation of AKT and AMPK levels. We concluded that a combination of BFOV and metformin ameliorates hepatic steatosis in HFC57 mice via alleviating hepatic inflammation and enhancing insulin signalling pathway, suggesting that the combination of BFOV and metformin is a potential treatment for hepatic steatosis.

Unraveling the binding mechanism of an Oxovanadium(IV) - Curcumin complex on albumin, DNA and DNA gyrase by in vitro and in silico studies and evaluation of its hemocompatibility.

An oxovanadium(IV) - curcumin based complex, viz. [VO(cur)(2,2´-bipy)(H2O)] where cur is curcumin and bipy is bipyridine, previously synthesized, has been studied for interaction with albumin and DNA. Fluorescence emission spectroscopy was used to evaluate the interaction of the complex with bovine serum albumin (BSA) and the BSA-binding constant (Kb) was calculated to be 2.56 x 105 M-1, whereas a single great-affinity binding site was revealed. Moreover, the hemocompatibility test demonstrated that the complex presented low hemolytic fraction (mostly below 1%), in all concentrations tested (0-250 µΜ of complex, 5% DMSO) assuring a safe application in interaction with blood. The binding of the complex to DNA was also investigated using absorption, fluorescence, and viscometry methods indicating a binding through a minor groove mode. From competitive studies with ethidium bromide the apparent binding constant value to DNA was estimated to be 4.82 x 106 M-1. Stern-Volmer quenching phenomenon gave a ΚSV constant [1.92 (± 0.05) x 104 M-1] and kq constant [8.33 (± 0.2) x 1011 M-1s-1]. Molecular docking simulations on the crystal structure of BSA, calf thymus DNA, and DNA gyrase, as well as pharmacophore analysis for BSA target, were also employed to study in silico the ability of [VO(cur)(2,2´-bipy)(H2O)] to bind to these target bio-macromolecules and explain the observed in vitro activity.

Catalytic Activity of New Oxovanadium(IV) Microclusters with 2-Phenylpyridine in Olefin Oligomerization.

So far, few microclusters containing vanadium have been described in the literature. In this report, the synthesis protocol for the preparation of oxovanadium (IV) microclusters with 2-phenylpyridine is shown for the first time. Moreover, the crystal structure of these microclusters is also studied through the use of X-rays. The morphology of the prepared crystals is investigated using a field-emission Scanning Electron Microscope (SEM). The new compound, after activation by modified methylaluminoxane as the catalytic system, is investigated regarding the oligomerizations of 3-buten-1-ol, 2-chloro-2-propen-1-ol, allyl alcohol, and 2,3-dibromo-2-propen-1-ol. The products of oligomerization are tested by the TG-FTIR and MALDI-TOF-MS methods. Moreover, the values of catalytic activities for the new oxovanadium(IV) microclusters with 2-phenylpyridine are determined for the 3-buten-1-ol, 2-chloro-2-propen-1-ol, allyl alcohol, and 2,3-dibromo-2-propen-1-ol oligomerizations. Oxovanadium(IV) microclusters with 2-phenylpyridine are shown to be very highly active precatalysts for the oligomerization of allyl alcohol, 2,3-dibromo-2-propen-1-ol, and 3-buten-1-ol. However, in the case of 2-chloro-2-propen-1-ol oligomerization, the new microclusters are seen as highly active precatalysts.

Novel Oxovanadium Complex VO(hntdtsc)(NPIP): Anticancer Activity and Mechanism of Action on HeLa Cells.

Oxovanadium complexes, particularly vanadyl (IV) derivatives with hybrid ligands of Schiff base and polypyridyl, have been demonstrated to possess great anticancerous therapeutic efficacy. However, most of the studies on the activity of these oxovanadium complexes have mainly focused on in vitro studies, and animal studies in vivo are extremely scarce. Based on the antitumor test results of four novel oxovanadium complexes in our previous work, this work further conducted a comprehensive antitumor activity study in vitro and in vivo on VO(hntdtsc)(NPIP), which owned the strongest inhibitory activity in vitro on multiple tumor cell proliferation. The cellular mechanism study suggested that VO(hntdtsc)(NPIP) inhibited the cell proliferation via arresting the cell cycle at G0/G1 phase through the p16-cyclin D1-CDK4-p-Rb pathway and inducing cell apoptosis through mitochondrial-dependent apoptosis pathway on HeLa cells. Inconsistent with the effects in vitro, VO(hntdtsc)(NPIP) significantly inhibited the growth of tumor and induced the apoptosis of cancer cells in mice xenograft models according to the results of nude mice in vivo image detection, H&E pathological examination, and immunohistochemical detection of p16/Ki-67 protein expression. Collectively, all the results, particularly studies in vivo, demonstrated that VO(hntdtsc)(NPIP) hold a potential to be the lead compound and further to be an anticervical cancer drug.

Green Synthesis of Oxovanadium(IV)/chitosan Nanocomposites and Its Ameliorative Effect on Hyperglycemia, Insulin Resistance, and Oxidative Stress.

In this paper, the preparation, characterization, and ameliorative effect on high-fat high-sucrose diet-induced hyperglycemia, insulin resistance, oxidative stress in mice of novel oxovanadium(IV)/chitosan (OV/CS) nanocomposites were investigated. The nanobiocomposite was produced by chemical reduction by chitosan and L-ascorbic acid using microwave heating, under environment-friendly conditions, using aqueous solutions, and notably, by using both mediators as reducing and stabilizing agents. In addition, OV/CS nanocomposites were characterized by transmission electron microscopy, energy dispersive spectroscopy, particle size, and zeta potential measurements. In vivo experiments were designed to examine whether the OV/CS nanocomposites would provide additional benefits on oxidative stress, hyperglycemia, and insulin resistance in mice with type 2 diabetes. The results rendered insulin resistant by treating with OV/CS nanocomposites alleviate insulin resistance and improve oxidative stress. Such nanocomposite seem to be a valuable therapy to achieve and/or maintain glycemic control and therapeutic agents in the treatment arsenal for insulin resistance and type 2 diabetes.

Inhibition of Src homology 2 domain-containing phosphatase 1 increases insulin sensitivity in high-fat diet-induced insulin-resistant mice.

Insulin resistance plays a crucial role in the development of type 2 diabetes. Insulin receptor signalling is antagonized and tightly controlled by protein tyrosine phosphatases (PTPs). However, the precise role of the PTP src homology 2 domain-containing phosphatase 1 (SHP-1) in insulin resistance has not been explored. Male C57BL/6J mice were fed a high-fat diet (HFD, 60% kcal from fat), to induce insulin resistance, or a low-fat diet (LFD, 10% kcal from fat) for 10 weeks. Afterwards, HFD-fed mice were pharmacologically treated with the SHP-1 (Ptpn6) inhibitor sodium stibogluconate and the broad spectrum pan-PTP inhibitor bis(maltolato)oxovanadium(IV) (BMOV). Both inhibitors ameliorated the metabolic phenotype, as evidenced by reduced body weight, improved insulin sensitivity and glucose tolerance, which was not due to altered PTP gene expression. In parallel, phosphorylation of the insulin receptor and of the insulin signalling key intermediate Akt was enhanced, and both PTP inhibitors and siRNA-mediated SHP-1 downregulation resulted in an increased glucose uptake in vitro. Finally, recombinant SHP-1 was capable of dephosphorylating the ligand-induced tyrosine-phosphorylated insulin receptor. These results indicate a central role of SHP-1 in insulin signalling during obesity, and SHP-1 inhibition as a potential therapeutic approach in metabolic diseases.

Bis(maltolato)oxovanadium(IV) (BMOV) Attenuates Apoptosis in High Glucose-Treated Cardiac Cells and Diabetic Rat Hearts by Regulating the Unfolded Protein Responses (UPRs).

Endoplasmic reticulum stress (ERS)-induced unfolded protein response (UPR) and the subsequent cell deaths are essential steps in the pathogenesis of diabetic cardiomyopathy (DCM), a main cause of diabetics' morbidity and mortalities. The bis(maltolato)oxovanadium(IV) (BMOV), a potent oral vanadium complex with anti-diabetic properties and insulin-mimicking effects, was shown to improve cardiac dysfunctions in diabetic models. Here, we examined the effects of BMOV on UPR pathway protein expression and apoptotic cell deaths in both high glucose-treated cardiac H9C2 cells and in the hearts of diabetic rats. We show that in both the high glucose-treated cardiac cells and in the hearts of streptozotocin (STZ) diabetic rats, there was an overall activation of the UPR signaling, including both apoptotic (e.g., the cascades of PERK/EIf2α/ATF4/CHOP and of IRE1/caspase 12/caspase 3) and pro-survival (GRP78 and XBP1) signaling. A high amount of apoptotic cell deaths was also detected in both diabetic conditions. The administration of BMOV suppressed both the apoptotic and pro-survival UPR signaling and significantly attenuated apoptotic cell deaths in both conditions. The overall suppression of UPR signaling by BMOV suggests that the drug protects diabetic cardiomyopathy by counteracting reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress. Our findings lend support to promote the use of BMOV in the treatment of diabetic heart diseases.