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1.
Sci Rep ; 14(1): 9545, 2024 04 25.
Artículo en Inglés | MEDLINE | ID: mdl-38664493

RESUMEN

An essential research area for scientists is the development of high-performing, inexpensive, non-toxic antibacterial materials that prevent the transfer of bacteria. In this study, pure Bi2WO6 and Bi2WO6/MWCNTs nanocomposite were prepared by hydrothermal method. A series of characterization results by using XRD FTIR, Raman, FESEM, TEM, and EDS analyses, reveal the formation of orthorhombic nanoflakes Bi2WO6 by the addition of NaOH and pH adjustment to 7. Compared to pure Bi2WO6, the Bi2WO6/MWCNTs nanocomposite exhibited that CNTs are efficiently embedded into the structure of Bi2WO6 which results in charge transfer between metal ion electrons and the conduction or valence band of Bi2WO6 and MWCNTs and result in shifting to longer wavelength as shown in UV-visible and PL. The results confirmed that MWCNTs are stuck to the surface of the microflowers, and some of them embedded inside the Bi2WO6 nanoflakes without affecting the structure of Bi2WO6 nanoflakes as demonstrated by TEM. In addition, Pure Bi2WO6 and the Bi2WO6/MWCNTs nanocomposite were tested against P. mirabilis and S. mutans., confirming the effect of addition MWCNTs materials had better antibacterial activity in opposition to both bacterial strains than pure Bi2WO6. Besides, pure Bi2WO6 and the Bi2WO6/MWCNTs nanocomposite tested for cytotoxicity against lung MTT test on Hep-G2 liver cancer cells, and flow-cytometry. Results indicated that pure Bi2WO6 and the Bi2WO6/MWCNTs nanocomposite have significant anti-cancer efficacy against Hep-G2 cells in vitro. In addition, the findings demonstrated that Bi2WO6 and Bi2WO6/MWCNTs triggered cell death via increasing ROS. Based on these findings, it appears that pure Bi2WO6 and the Bi2WO6/MWCNTs nanocomposite have the potential to be developed as nanotherapeutics for the treatment of bacterial infections, and liver cancer.


Asunto(s)
Antibacterianos , Antineoplásicos , Bismuto , Nanocompuestos , Compuestos de Tungsteno , Nanocompuestos/química , Antibacterianos/farmacología , Antibacterianos/química , Humanos , Antineoplásicos/farmacología , Antineoplásicos/química , Bismuto/química , Bismuto/farmacología , Compuestos de Tungsteno/química , Compuestos de Tungsteno/farmacología , Nanotubos de Carbono/química , Pruebas de Sensibilidad Microbiana , Supervivencia Celular/efectos de los fármacos , Células Hep G2
2.
ACS Appl Mater Interfaces ; 16(17): 21546-21556, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38626342

RESUMEN

Radiodynamic therapy (RDT) has emerged as a promising modality for cancer treatment, offering notable advantages such as deep tissue penetration and radiocatalytic generation of oxygen free radicals. However, the oxygen-dependent nature of RDT imposes limitations on its efficacy in hypoxic conditions, particularly in modulating and eliminating radioresistant immune suppression cells. A novel approach involving the creation of a "super" tetrahedron polyoxometalate (POM) cluster, Fe12-POM, has been developed for radiation boosted chemodynamic catalysis to enable oxygen-independent RDT in hypoxic conditions. This nanoscale cluster comprises four P2W15 units functioning as energy antennas, while the Fe3 core serves as an electron receptor and catalytic center. Under X-ray radiation, a metal-to-metal charge transfer phenomenon occurs between P2W15 and the Fe3 core, resulting in the valence transition of Fe3+ to Fe2+ and a remarkable 139-fold increase in hydroxyl radical generation compared to Fe12-POM alone. The rapid generation of hydroxyl radicals, in combination with PD-1 therapy, induces a reprogramming of the immune environment within tumors. This reprogramming is characterized by upregulation of CD80/86, downregulation of CD163 and FAP, as well as the release of interferon-γ and tumor necrosis factor-α. Consequently, the occurrence of abscopal effects is facilitated, leading to significant regression of both local and distant tumors in mice. The development of oxygen-independent RDT represents a promising approach to address cancer recurrence and improve treatment outcomes.


Asunto(s)
Microambiente Tumoral , Animales , Ratones , Humanos , Microambiente Tumoral/efectos de los fármacos , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Neoplasias/inmunología , Oxígeno/química , Compuestos de Tungsteno/química , Compuestos de Tungsteno/farmacología , Línea Celular Tumoral
3.
Int J Mol Sci ; 24(10)2023 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-37240203

RESUMEN

The present study presents the tertiary assembly of a POM, peptide, and biogenic amine, which is a concept to construct new hybrid bio-inorganic materials for antibacterial applications and will help to promote the development of antivirus agents in the future. To achieve this, a Eu-containing polyoxometalate (EuW10) was first co-assembled with a biogenic amine of spermine (Spm), which improved both the luminescence and antibacterial effect of EuW10. Further introduction of a basic peptide from HPV E6, GL-22, induced more extensive enhancements, both of them being attributed to the cooperation and synergistic effects between the constituents, particularly the adaptive responses of assembly to the bacterial microenvironment (BME). Further intrinsic mechanism investigations revealed in detail that the encapsulation of EuW10 in Spm and further GL-22 enhanced the uptake abilities of EuW10 in bacteria, which further improved the ROS generation in BME via the abundant H2O2 involved there and significantly promoted the antibacterial effects.


Asunto(s)
Peroxidasa , Compuestos de Tungsteno , Compuestos de Tungsteno/farmacología , Peróxido de Hidrógeno , Péptidos , Colorantes , Antibacterianos/farmacología
4.
Angew Chem Int Ed Engl ; 61(41): e202210019, 2022 10 10.
Artículo en Inglés | MEDLINE | ID: mdl-35975881

RESUMEN

Herein, a giant Sb-rich polyoxometalate (POM) {Sb21 Tb7 W56 } is reported, which contains the largest number of Sb atoms in a POM so far. The Sb-rich POM has many interesting structural features and is a rare example of a soluble and water-stable giant POM. Biomedical studies indicate that the Sb-rich POM exhibits broad-spectrum antitumor activity against various cancer cell lines by reactivating the P53-dependent apoptotic processes and disrupting the mitochondrial membrane. In addition, this Sb-rich POM was capable of suppressing the growth and metastasis of a breast cancer in vivo. This work demonstrates that Sb-rich POMs are promising candidates for the development of new anticancer drugs.


Asunto(s)
Antineoplásicos , Compuestos de Tungsteno , Aniones , Antimonio/farmacología , Antineoplásicos/química , Antineoplásicos/farmacología , Humanos , Polielectrolitos , Proteína p53 Supresora de Tumor , Compuestos de Tungsteno/química , Compuestos de Tungsteno/farmacología , Agua
5.
Int J Mol Sci ; 23(15)2022 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-35897839

RESUMEN

Polyoxometalate nanoparticles (POMs) are a class of compounds made up of multiple transition metals linked together using oxygen atoms. POMs commonly include group 6 transition metals, with two of the most common forms using molybdenum and tungsten. POMs are suggested to exhibit antimicrobial effects. In this study, we developed two POM preparations to study anti-cancer activity. We found that Mo-POM (NH4)Mo7O24) and W-POM (H3PW12O40) have anti-cancer effects on glioblastoma cells. Both POMs induced morphological changes marked by membrane swelling and the presence of multinucleated cells that may indicate apoptosis induction along with impaired cell division. We also observed significant increases in lipid oxidation events, suggesting that POMs are redox-active and can catalyze detrimental oxidation events in glioblastoma cells. Here, we present preliminary indications that molybdenum polyoxometalate nanoparticles may act like ferrous iron to catalyze the oxidation of phospholipids. These preliminary results suggest that Mo-POMs (NH4)Mo7O24) and W-POMs (H3PW12O40) may warrant further investigation into their utility as adjunct cancer therapies.


Asunto(s)
Glioblastoma , Nanopartículas , Elementos de Transición , Compuestos de Tungsteno , Aniones , Muerte Celular , Glioblastoma/tratamiento farmacológico , Humanos , Lípidos , Molibdeno/farmacología , Polielectrolitos , Compuestos de Tungsteno/farmacología
6.
J Biol Inorg Chem ; 27(4-5): 405-419, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35713714

RESUMEN

As shown in studies conducted in recent decades, polyoxometalates (POMs), as inorganic metal oxides, have promising biological activities, including antitumor, anti-infectious and anti-Alzheimer's activities, due to their special structures and properties. However, some side effects impede their clinical applications to a certain extent. Compared with unmodified POMs, POM-based inorganic-organic hybrids and POM-based nanocomposite structures show significantly enhanced bioactivity and reduced side effects. In this review, we introduce the biological activities of POMs and their derivatives and highlight the side effects of POMs on normal cells and organisms and their possible mechanisms of action. We then propose a development direction for overcoming their side effects. POMs are expected to constitute a new generation of inorganic metal drugs for the treatment of cancer, infectious diseases, and Alzheimer's disease.Graphical abstract.


Asunto(s)
Enfermedad de Alzheimer , Enfermedades Transmisibles , Neoplasias , Compuestos de Tungsteno , Enfermedad de Alzheimer/tratamiento farmacológico , Aniones , Humanos , Neoplasias/tratamiento farmacológico , Polielectrolitos , Compuestos de Tungsteno/química , Compuestos de Tungsteno/farmacología , Compuestos de Tungsteno/uso terapéutico
7.
J Inorg Biochem ; 226: 111654, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34740036

RESUMEN

Here we show that Preyssler-type polyoxotungstates (Preyssler-type POTs, [NaP5W30O110]-14) complexed with peptides can prevent the dysbiotic expansion of anaerobic bacteria of the Enterobacteriaceae family. In a dextran sulfate sodium (DSS)-induced colitis model, symptom remission of C57BL/6 J mice with colitis is achieved by orally treated with POT complexes. Ten days of daily administration of POT complexes reduces 5% body weight loss and the mRNA levels of proinflammatory markers (77% reduction for Il6, 73% reduction for Tnf, 91% reduction for Cxcl1) in the caecum and proximal colon. Bacterial population analysis reveals that these Enterobacteriaceae population in the caecal content decline by one order of magnitude after administration of POT complexes. POT complexes exert anti-inflammatory effects indirectly on the host immune system by inhibition of malignant expansion of anaerobic Enterobacteriaceae during gut inflammation. Furthermore, POTs show negligible effect on bacterial growth in vitro, healthy mice and their microbiota composition under homeostatic conditions. Rationally designed POT complexes will provide distinctive approach to improve enteric bacteria dysbiosis-associated gut inflammation by balancing bacterial communities.


Asunto(s)
Colitis , Sulfato de Dextran/toxicidad , Disbiosis , Enterobacteriaceae/crecimiento & desarrollo , Compuestos de Tungsteno/farmacología , Animales , Ciego/microbiología , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Colitis/microbiología , Colon/microbiología , Modelos Animales de Enfermedad , Disbiosis/inducido químicamente , Disbiosis/tratamiento farmacológico , Disbiosis/microbiología , Ratones
8.
Sci Rep ; 11(1): 19354, 2021 09 29.
Artículo en Inglés | MEDLINE | ID: mdl-34588468

RESUMEN

In order to elucidate the active polyoxotungstate (POT) species that inhibit fungal polyphenol oxidase (AbPPO4) in sodium citrate buffer at pH 6.8, four Wells-Dawson phosphotungstates [α/ß-PV2WVI18O62]6- (intact form), [α2-PV2WVI17O61]10- (monolacunary), [PV2WVI15O56]12- (trilacunary) and [H2PV2WVI12O48]12- (hexalacunary) were investigated. The speciation of the POT solutions under the dopachrome assay (50 mM Na-citrate buffer, pH 6.8; L-3,4-dihydroxyphenylalanine as a substrate) conditions were determined by 183W-NMR, 31P-NMR spectroscopy and mass spectrometry. The intact Wells-Dawson POT [α/ß-PV2WVI18O62]6- shows partial (~ 69%) disintegration into the monolacunary [α2-PV2WVI17O61]10- anion with moderate activity (Ki = 9.7 mM). The monolacunary [α2-PV2WVI17O61]10- retains its structural integrity and exhibits the strongest inhibition of AbPPO4 (Ki = 6.5 mM). The trilacunary POT [PV2WVI15O56]12- rearranges to the more stable monolacunary [α2-PV2WVI17O61]10- (~ 62%) accompanied by release of free phosphates and shows the weakest inhibition (Ki = 13.6 mM). The hexalacunary anion [H2PV2WVI12O48]12- undergoes time-dependent hydrolysis resulting in a mixture of [H2PV2WVI12O48]12-, [PV8WVI48O184]40-, [PV2WVI19O69(H2O)]14- and [α2-PV2WVI17O61]10- which together leads to comparable inhibitory activity (Ki = 7.5 mM) after 48 h. For the solutions of [α/ß-PV2WVI18O62]6-, [α2-PV2WVI17O61]10- and [PV2WVI15O56]12- the inhibitory activity is correlated to the degree of their rearrangement to [α2-PV2WVI17O61]10-. The rearrangement of hexalacunary [H2PV2WVI12O48]12- into at least four POTs with a negligible amount of monolacunary anion interferes with the correlation of activity to the degree of their rearrangement to [α2-PV2WVI17O61]10-. The good inhibitory effect of the Wells-Dawson [α2-PV2WVI17O61]10- anion is explained by the low charge density of its protonated forms Hx[α2-PV2WVI17O61](10-x)- (x = 3 or 4) at pH 6.8.


Asunto(s)
Agaricus/enzimología , Proteínas Fúngicas/antagonistas & inhibidores , Monofenol Monooxigenasa/antagonistas & inhibidores , Compuestos de Tungsteno/farmacología , Espectroscopía de Resonancia Magnética , Estructura Molecular , Monofenol Monooxigenasa/ultraestructura , Espectrometría de Masa por Ionización de Electrospray , Compuestos de Tungsteno/química
9.
Int J Mol Sci ; 22(14)2021 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-34299098

RESUMEN

BACKGROUND: This study was designed to investigate the effect of cluster differentiation (CD)39 and CD73 inhibitors on the expresion of tumour-associated macrophages (TAMs), M1- versus M2-tumour phenotypes in mice with colon cancer. METHODS: An in vivo study of co-culture with colon cancer cells and immune cells from the bone marrow (BM) of mice was performed. After the confirmation of the effect of polyoxotungstate (POM-1) as an inhibitor of CD39 on TAMs, the mice were randomly divided into a control group without POM-1 and a study group with POM-1, respectively, after subcutaneous injection of CT26 cells. On day 14 after the injection, the mice were sacrificed, and TAMs were evaluated using fluorescence-activated cell sorting. RESULTS: In the in vivo study, the co-culture with POM-1 significantly increased the apoptosis of CT26 cells. The cell population from the co-culture with POM-1 showed significant increases in the expression of CD11b+ for myeloid cells, lymphocyte antigen 6 complex, locus C (Ly6C+) for monocytes, M1-tumour phenotypes from TAMs, and F4/80+ for macrophages. In the in vivo study, tumour growth in the study group with POM-1 was significantly limited, compared with the control group without POM-1. The expressions of Ly6C+ and major histocompatibility complex class II+ for M1-tumour phenotypes from TAMs on F4/80+ from the tumour tissue in the study group had significantly higher values compared with the control group. CONCLUSION: The inhibition of CD39 with POM-1 prevented the growth of colon cancer in mice, and it was associated with the increased expression of M1-tumour phenotypes from TAMs in the cancer tissue.


Asunto(s)
Apirasa/antagonistas & inhibidores , Neoplasias del Colon/prevención & control , Polímeros/farmacología , Macrófagos Asociados a Tumores/efectos de los fármacos , Compuestos de Tungsteno/farmacología , Animales , Antígenos CD , Apoptosis , Proliferación Celular , Neoplasias del Colon/metabolismo , Neoplasias del Colon/patología , Humanos , Ratones , Ratones Endogámicos BALB C , Pronóstico , Células Tumorales Cultivadas , Macrófagos Asociados a Tumores/metabolismo , Macrófagos Asociados a Tumores/patología , Ensayos Antitumor por Modelo de Xenoinjerto
10.
Angew Chem Int Ed Engl ; 60(39): 21449-21456, 2021 09 20.
Artículo en Inglés | MEDLINE | ID: mdl-34314545

RESUMEN

We successfully synthesized {BiW8 }, a 10-nuclear heteroatom cluster modified {BiW8 O30 }. At 24 h post-incubation, the IC50 values of {BiW8 } against HUVEC, MG63, RD, Hep3B, HepG2, and MCF7 cells were 895.8, 127.3, 344.3, 455.0, 781.3, and 206.3 µM, respectively. The IC50 value of {BiW8 } on the MG63 cells was more than 2-fold lower than that of the other raw materials. Through morphological and functional features, we demonstrated pyroptosis as a newly identified mechanism of cell death induced by {BiW8 }. {BiW8 } increased 2-fold reactive oxygen species (ROS) levels in MG63 cells at 24 h post-incubation. Compared with 0 h, the glutathione (GSH) content decreased by 59, 65, 75, 94, and 97 % at 6, 12, 24, 36 and 48 h post-incubation, respectively. Furthermore, multiple antitumor mechanisms of {BiW8 } were identified via transcriptome analysis and chemical simulation, including activation of pyroptosis, suppression of GSH generation, depletion of GSH, and inhibition of DNA repair.


Asunto(s)
Antineoplásicos/farmacología , Piroptosis/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Compuestos de Tungsteno/farmacología , Regulación hacia Arriba/efectos de los fármacos , Antineoplásicos/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Compuestos de Tungsteno/química
11.
ACS Appl Mater Interfaces ; 13(23): 26721-26734, 2021 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-34080430

RESUMEN

Pro-inflammatory and amyloidogenic S100A9 protein is central to the amyloid-neuroinflammatory cascade in neurodegenerative diseases. Polyoxometalates (POMs) constitute a diverse group of nanomaterials, which showed potency in amyloid inhibition. Here, we have demonstrated that two selected nanosized niobium POMs, Nb10 and TiNb9, can act as potent inhibitors of S100A9 amyloid assembly. Kinetics analysis based on ThT fluorescence experiments showed that addition of either Nb10 or TiNb9 reduces the S100A9 amyloid formation rate and amyloid quantity. Atomic force microscopy imaging demonstrated the complete absence of long S100A9 amyloid fibrils at increasing concentrations of either POM and the presence of only round-shaped and slightly elongated aggregates. Molecular dynamics simulation revealed that both Nb10 and TiNb9 bind to native S100A9 homo-dimer by forming ionic interactions with the positively charged Lys residue-rich patches on the protein surface. The acrylamide quenching of intrinsic fluorescence showed that POM binding does not perturb the Trp 88 environment. The far and near UV circular dichroism revealed no large-scale perturbation of S100A9 secondary and tertiary structures upon POM binding. These indicate that POM binding involves only local conformational changes in the binding sites. By using intrinsic and 8-anilino-1-naphthalene sulfonate fluorescence titration experiments, we found that POMs bind to S100A9 with a Kd of ca. 2.5 µM. We suggest that the region, including Lys 50 to Lys 54 and characterized by high amyloid propensity, could be the key sequences involved in S1009 amyloid self-assembly. The inhibition and complete hindering of S100A9 amyloid pathways may be used in the therapeutic applications targeting the amyloid-neuroinflammatory cascade in neurodegenerative diseases.


Asunto(s)
Amiloide/antagonistas & inhibidores , Calgranulina B/química , Calgranulina B/metabolismo , Enfermedades Neurodegenerativas , Compuestos de Tungsteno/farmacología , Humanos , Conformación Proteica
12.
Dalton Trans ; 50(23): 8076-8083, 2021 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-34018508

RESUMEN

A multifunctional supramolecular complex is reported for the integrated multiple magnetic resonance imaging/computed X-ray tomography (MRI/CT) imaging and photothermal therapy, wherein a gadolinium-substituted paramagnetic polyoxometalate cluster and food-borne antioxidant peptides identified from the trepang protein hydrolysates are introduced. The as-prepared complex maintained an uniform particle size and much better biocompatibility, and is an ideal candidate for the in vivo applications. The complex allows for T1-weighted MR imaging and a high Hounsfield unit value for enhanced CT imaging. Interestingly, we demonstrate that the complex possesses outstanding photothermal cancer-killing effects due to its high photothermal conversion efficiency under the exposure of an NIR laser and enhanced antibacterial activity to avoid bacterial infection from the thermal therapeutic process. These results indicate that the supramolecular complex platform exhibit potential for accurate medical diagnosis at an early stage and effective eradication of the tumor cells.


Asunto(s)
Antibacterianos/farmacología , Antineoplásicos/farmacología , Gadolinio/farmacología , Péptidos/farmacología , Terapia Fototérmica , Compuestos de Tungsteno/farmacología , Antibacterianos/síntesis química , Antibacterianos/química , Antineoplásicos/síntesis química , Antineoplásicos/química , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Escherichia coli/efectos de los fármacos , Gadolinio/química , Humanos , Rayos Infrarrojos , Sustancias Macromoleculares/síntesis química , Sustancias Macromoleculares/química , Sustancias Macromoleculares/farmacología , Imagen por Resonancia Magnética , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Péptidos/síntesis química , Péptidos/química , Tomografía Computarizada por Rayos X , Células Tumorales Cultivadas , Compuestos de Tungsteno/química
13.
Eur J Pharmacol ; 905: 174198, 2021 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-34033815

RESUMEN

CD39 is associated with diverse physiological and pathological processes, including cell proliferation and differentiation. Adenosine triphosphate (ATP) is hydrolysed to adenosine by different enzymes including ecto-nucleoside triphosphate diphosphohydrolase-1/ENTPD1 (CD39) and ecto-5'-nucleotidase (CD73), regulating many physiological and pathological processes in various diseases, but these changes and functions in alcoholic liver disease are generally unknown. In this study, an alcoholic liver disease model in vivo was induced by ethanol plus carbon tetrachloride(CCl4) administered to C57BL/6 mice, who were the intraperitoneally injected with the CD39 inhibitor sodium polyoxotungstate (POM1) or colchicine from the 5th week to the 8th week. Meanwhile, hepatic stellate cells were stimulated by acetaldehyde to replicate alcoholic liver fibrosis models in vitro. Exogenous ATP and POM1 were added in turn to the culture system. Pharmacological blockade of CD39 largely prevents liver damage and collagen deposition. We found that blockade or silencing of CD39 prevented acetaldehyde-induced proliferation of HSC-T6 cells and the expression of fibrogenic factors. Moreover, blockade or silencing of CD39 could block the activation of the adenosine A2A and adenosine A2B receptors and the TGF-ß/Smad3 pathway, which are essential events in HSC activation. Thus, blockade of CD39 to inhibit the transduction of ATP to adenosine may prevent HSC activation, alleviating alcoholic hepatic fibrosis. The findings from this study suggest ATP-adenosine signalling is a novel therapeutic and preventive target for alcoholic liver disease.


Asunto(s)
Adenosina Trifosfato/metabolismo , Adenosina/metabolismo , Antígenos CD/metabolismo , Apirasa/metabolismo , Células Estrelladas Hepáticas/metabolismo , Hepatopatías Alcohólicas/etiología , Hepatopatías Alcohólicas/metabolismo , Transducción de Señal/efectos de los fármacos , 5'-Nucleotidasa/genética , 5'-Nucleotidasa/metabolismo , Acetaldehído/toxicidad , Animales , Antígenos CD/genética , Apirasa/antagonistas & inhibidores , Apirasa/genética , Tetracloruro de Carbono/toxicidad , Colchicina/farmacología , Citocinas/metabolismo , Modelos Animales de Enfermedad , Etanol/toxicidad , Técnicas de Silenciamiento del Gen , Humanos , Hepatopatías Alcohólicas/patología , Ratones Endogámicos C57BL , Cultivo Primario de Células , Ratas , Receptor de Adenosina A2A/metabolismo , Receptor de Adenosina A2B/metabolismo , Proteína smad3/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Compuestos de Tungsteno/farmacología
14.
J Inorg Biochem ; 220: 111463, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33894505

RESUMEN

Developing strategies against the antibiotic resistance is a major global challenge for public health. Here, we report the synergy of the combination of Preyssler-type polyoxometalates (POMs) ([NaP5W30O110]14- or [AgP5W30O110]14-) and ribosome-targeting antibiotics for high antibacterial efficiency with low risk of antibiotic resistance. Due to their ultra-small sizes and active surface ligands, POM anions show strong affinity to bacterial cell membrane and impose hyperpolarization of the bacterial cells as well as the decrease of Mg2+ influx by blocking Mg2+ transporters, which finally lead to the structural perturbations of ribosomes and instability of bacterial structures. The bacterial growth can, therefore, be regulated by the presence of POMs: a fraction of Bacillus subtilis shifted to a 'dormant', slow-growing cellular state (an extended lag phase) upon the application of subinhibitory concentration of POMs. An approach to combat antibiotic resistant bacteria by applying POMs at their early growth phase followed by antibiotic exposure is validated, and its high efficiency for bacterial control is confirmed.


Asunto(s)
Antibacterianos/farmacología , Farmacorresistencia Bacteriana/efectos de los fármacos , Compuestos de Tungsteno/farmacología , Bacillus subtilis/efectos de los fármacos , Membrana Celular/efectos de los fármacos , Sinergismo Farmacológico , Magnesio/metabolismo , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Pasteurellaceae/efectos de los fármacos , Espectinomicina/farmacología
15.
Biometals ; 34(1): 107-117, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33180255

RESUMEN

Octyltrimethylammonium tetrathiotungstate salt (ATT-C8) was synthesized and its ability to chelate copper was evaluated. The biological and toxic aspects were evaluated by in vitro and in vivo assays, using bovine aorta endothelial cells (BAEC) and zebrafish (Danio rerio) embryos. The obtained results suggest that ATT-C8 has better biocompatibility, showing a significantly lower lethal concentration 50 (LC50) value in comparison to ammonium tetrathiotungstate (ATT). Zebrafish embryos assay results indicate that both tetrathiotungstate salts at the studied concentrations increase the hatching time. Even more, an in vivo assay showed that synthesized materials behave as copper antagonists and have the ability to inhibit its toxicological effects. Also, both materials were found to be active for the in vitro 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The characterization of the materials was carried out using the following spectroscopic techniques: Ultraviolet-Visible (UV-Vis), Fourier Transform Infrared (FTIR) and proton nuclear magnetic resonance (1H-NRM).


Asunto(s)
Antioxidantes/farmacología , Compuestos de Amonio Cuaternario/farmacología , Compuestos de Tungsteno/farmacología , Antioxidantes/síntesis química , Antioxidantes/química , Compuestos de Bifenilo/antagonistas & inhibidores , Estructura Molecular , Picratos/antagonistas & inhibidores , Compuestos de Amonio Cuaternario/síntesis química , Compuestos de Amonio Cuaternario/química , Compuestos de Tungsteno/síntesis química , Compuestos de Tungsteno/química
16.
Molecules ; 25(24)2020 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-33353184

RESUMEN

Fungal infections pose a serious threat to human health. Polyoxometalates (POMs) are metal-oxygen clusters with potential application in the control of microbial infections. Herein, the Ag3PW12O40 composites have been synthesized and verified by Fourier transform infrared (FT-IR) spectrum, transmission electron microscopy (TEM), scanning electron microscope (SEM), elemental analysis, and X-ray diffraction (XRD). The antifungal activities of Ag3PW12O40 were screened in 19 Candida species strains through the determination of minimum inhibitory concentration (MIC) by the microdilution checkerboard technique. The minimum inhibitory concentration (MIC50) values of Ag3PW12O40 are 2~32 µg/mL to the Candida species. The MIC80 value of Ag3PW12O40 to resistant clinical isolates C. albicans HL963 is 8 µg/mL, which is lower than the positive control, fluconazole (FLC). The mechanism against C. albicans HL963 results show that Ag3PW12O40 can decrease the ergosterol content. The expressions of ERG1, ERG7, and ERG11, which impact on the synthesis of ergosterol, are all prominently upregulated by Ag3PW12O40. It indicates that Ag3PW12O40 is a candidate in the development of new antifungal agents.


Asunto(s)
Antifúngicos/farmacología , Candida/efectos de los fármacos , Fósforo/farmacología , Plata/farmacología , Compuestos de Tungsteno/farmacología , Antifúngicos/química , Candida/crecimiento & desarrollo , Farmacorresistencia Fúngica/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Tamaño de la Partícula , Fósforo/química , Plata/química , Propiedades de Superficie , Compuestos de Tungsteno/química
17.
Molecules ; 25(23)2020 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-33271794

RESUMEN

Moulds inhabiting mineral-based materials may cause their biodeterioration, contributing to inestimable losses, especially in the case of cultural heritage objects and architectures. Fungi in mouldy buildings may also pose a threat to human health and constitute the main etiological factor in building related illnesses. In this context, research into novel compounds with antifungal activity is of high importance. The aim of this study was to evaluate the antifungal activity of polyoxometalate-ionic liquids (POM-ILs) and their use in the eradication of moulds from historical brick. In the disc diffusion assay, all the tested POM-ILs inhibited growth of a mixed culture of moulds including Engyodontium album, Cladosporium cladosporioides, Alternaria alternata and Aspergillus fumigatus. These were isolated from the surfaces of historical brick barracks at the Auschwitz II-Birkenau State Museum in Oswiecim, Poland. POM-IL coatings on historical brick samples, under model conditions, showed that two compounds demonstrated very high antifungal activity, completely limiting mould growth and development. The antifungal activity of the POM-ILs appeared to stem from their toxic effects on conidia, as evidenced by environmental scanning transmission electron microscopy observations. The results herein indicated that POM-ILs are promising disinfectant materials for use not only on historical objects, but probably also on other mineral-based materials.


Asunto(s)
Antifúngicos/farmacología , Materiales de Construcción/microbiología , Desinfectantes/farmacología , Hongos/crecimiento & desarrollo , Líquidos Iónicos , Compuestos de Tungsteno/farmacología , Hongos/efectos de los fármacos
18.
Theranostics ; 10(22): 10031-10045, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32929332

RESUMEN

Backgroud: Nowadays, biofilms that are generated as a result of antibiotic abuse cause serious threats to global public health. Such films are the primary factor that contributes to the failure of antimicrobial treatment. This is due to the fact that the films prevent antibiotic infiltration, escape from innate immune attacks by phagocytes and consequently generate bacterial resistance. Therefore, exploiting novel antibacterial agents or strategies is extremely urgent. Methods: Herein, we report a rational construction of a novel biofilm microenvironment (BME)-responsive antibacterial platform that is based on tungsten (W)-polyoxometalate clusters (POMs) to achieve efficient bactericidal effects. Results: On one hand, the acidity and reducibility of a BME could lead to the self-assembly of POMs to produce large aggregates, which favor biofilm accumulation and enhance photothermal conversion under near-infrared (NIR) light irradiation. On the other hand, reduced POM aggregates with BME-induced photothermal-enhanced efficiency also exhibit surprisingly high peroxidase-like activity in the catalysis of bacterial endogenous hydrogen peroxide (H2O2) to produce abundant reactive oxygen species (ROS). This enhances biofilm elimination and favors antibacterial effects. Most importantly, reduced POMs exhibit the optimal peroxidase-like activity in an acidic BME. Conclusion: Therefore, in addition to providing a prospective antibacterial agent, intelligent acid/reductive dual-responsive POMs will establish a new representative paradigm for the areas of healthcare with minimal side effects.


Asunto(s)
Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Biopelículas/efectos de los fármacos , Microambiente Celular/efectos de los fármacos , Nanopartículas/administración & dosificación , Compuestos de Tungsteno/farmacología , Cicatrización de Heridas/efectos de los fármacos , Animales , Bacterias/metabolismo , Femenino , Peróxido de Hidrógeno/metabolismo , Ratones , Ratones Endogámicos BALB C , Nanopartículas/química , Peroxidasa/metabolismo , Especies Reactivas de Oxígeno/metabolismo
19.
Planta ; 252(2): 22, 2020 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-32676756

RESUMEN

MAIN CONCLUSION: In Medicago sativa nodulated roots, NR-dependent NO production is involved in maintaining energy state, presumably through phytoglobin NO respiration, under both salinity and hypoxia stress. The response to low and average salinity stress and to a 5 day-long flooding period was analyzed in M. sativa nodulated roots. The two treatments result in a decrease in the biological nitrogen fixation capacity and the energy state (evaluated by the ATP/ADP ratio), and conversely in an increase nitric oxide (NO) production. Under salinity and hypoxia treatments, the use of either sodium tungstate, an inhibitor of nitrate reductase (NR), or carboxy-PTIO, a NO scavenger, results in a decrease in NO production and ATP/ADP ratio, meaning that NR-dependent NO production participates to the maintenance of the nodulated roots energy state.


Asunto(s)
Metabolismo Energético , Medicago sativa/fisiología , Nitrato-Reductasa/antagonistas & inhibidores , Óxido Nítrico/metabolismo , Fijación del Nitrógeno , Oxígeno/metabolismo , Medicago sativa/efectos de los fármacos , Medicago sativa/enzimología , Proteínas de Plantas/antagonistas & inhibidores , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/enzimología , Raíces de Plantas/fisiología , Nódulos de las Raíces de las Plantas/efectos de los fármacos , Nódulos de las Raíces de las Plantas/enzimología , Nódulos de las Raíces de las Plantas/fisiología , Salinidad , Compuestos de Tungsteno/farmacología , Agua/fisiología
20.
J Inorg Biochem ; 210: 111131, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32563103

RESUMEN

In this article, two Keggin-type polyoxometalates [Co(L)2]3[PMo12O40] (1) and [Co(L)2]3[PW12O40] (2) (HL = 2-acetylpyrazine thiosemicarbazone) were prepared and fully characterized. The compounds are stable in aqueous solution with different pH values and show superior antibacterial activity against Escherichia coli (E. coli: minimal inhibitory concentration (MIC) = 0.00375, 0.12 µg/mL), Agrobacterium tumefaciens (A. tumefaciens: MIC = 0.06, 0.12 µg/mL), Bacillus subtilis (B. subtilis: MIC = 0.015, 0.06 µg/mL) and especially for Staphylococcus aureus (S. aureus: MIC = 0.00048, 0.015 µg/mL) for 1 and 2, respectively. The time kill studies showed the entire killing of specific bacteria during 4 to 8 h. In addition, the possible antibacterial mechanism of compound 1 was explored systematically. The experimental results proved that cell wall/membrane damage, leakage of protein, inhibition of respiratory chain dehydrogenases activity, enhancement of intracellular reactive oxygen species (ROS) and depletion of glutathione (GSH) were the potential causes of bacteria death.


Asunto(s)
Antibacterianos/farmacología , Complejos de Coordinación/farmacología , Molibdeno/química , Compuestos de Tungsteno/farmacología , Antibacterianos/síntesis química , Bacterias/efectos de los fármacos , Membrana Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Cobalto/química , Complejos de Coordinación/síntesis química , Glutatión/metabolismo , Pruebas de Sensibilidad Microbiana , NADH Deshidrogenasa/antagonistas & inhibidores , Especies Reactivas de Oxígeno/metabolismo , Compuestos de Tungsteno/síntesis química
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