Browsing by Author "Gumerova, Nadiia I."
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- Inhibition of SERCA and PMCA Ca2+-ATPase activities by polyoxotungstatesPublication . Aureliano, Manuel; Fraqueza, Gil; Berrocal, Maria; Cordoba-Granados, Juan J.; Gumerova, Nadiia I.; Rompel, Annette; Gutierrez-Merino, Carlos; Mata, Ana M.Plasma membrane calcium ATPases (PMCA) and sarco(endo) reticulum calcium ATPases (SERCA) are key proteins in the maintenance of calcium homeostasis. Herein, we compare for the first time the inhibition of SERCA and PMCA calcium pumps by several polyoxotungstates (POTs), namely by Wells-Dawson phospho-tungstate anions [P2W18O62]6-(intact, {P2W18}), [P2W17O61]10-(monolacunary, {P2W17}), [P2W15O56]12-(trilacunary, {P2W15}), [H2P2W12O48]12-(hexalacunary, {P2W12}), [H3P2W15V3O62]6- (trivanadium-substituted, {P2W15V3}) and by Preyssler-type anion [NaP5W30O110]14-({P5W30}). The speciation in the solu-tions of tested POTs was investigated by 31P and 51V NMR spectroscopy. The tested POTs inhibited SERCA Ca2+- ATPase activity, whereby the Preyssler POT showed the strongest effect, with an IC50 value of 0.37 mu M. For {P2W17} and {P2W15V3} higher IC50 values were determined: 0.72 and 0.95 mu M, respectively. The studied POTs showed to be more potent inhibitors of PMCA Ca2+-ATPase activity, with lower IC50 values for {P2W17}, {P5W30} and {P2W15V3}.
- Polyoxidovanadates' interactions with proteins: an overviewPublication . Aureliano, Manuel; Gumerova, Nadiia I.; Sciortino, Giuseppe; Garribba, Eugenio; McLauchlan, Craig C.; Rompel, Annette; Crans, Debbie C.Polyoxidovanadates (POVs, previously named polyoxovanadates) are a subgroup of polyoxidometalates (POMs, previously named polyoxometalates) with interesting pharmacological actions that have been tested as potential antidiabetic, antibacterial, antiprotozoal, antiviral, and anticancer drugs. They contain mainly vanadium and are able to interact with proteins, affecting various biological processes. The most studied POV is the isopolyoxidovanadate decavanadate (V-10), which interacts with proteins and/or enzymes such as tyrosine protein phosphatases, P-type ATPases, RNA triphosphatases, myosin and actin. However, in many POVs-protein systems, the binding sites and/or the residues involved in the interaction are not identified. In the present review, the interactions of POVs, as well as linear trivanadate (V-3), both linear and cyclic tetravanadate (V-4) and two proposed heptavanadate (V-7; which are better described by V-10 molecules), with proteins are described through X-ray crystallographic studies. Interactions with POVs through theoretical and spectroscopic studies of proteins related to muscle contraction, serum, oxidative stress, and diabetes were also discussed. In sum, herein, we describe POVs' interactions with various proteins including acid phosphatase A, receptor tyrosine kinase, ectonucleoside triphosphate diphosphohydrolase (NTPDases), transient receptor potential cation channel (TRPM4), phosphoglucomutases, P-type ATPases, myosin, actin, transferrin, albumin, and glucosidases, among others. The putative POVs' effects on proteins are impacted by the POV' stability and speciation. The modes of POVs' interactions include H-bond, electrostatic, H-bond + electrostatic, van der Waals, and covalent binding. The spectroscopic, X-ray and computational results, the sites and modes of binding are described in detail. (C) 2021 The Authors. Published by Elsevier B.V
- Polyoxovanadates with emerging biomedical activitiesPublication . Aureliano, Manuel; Gumerova, Nadiia I.; Sciortino, Giuseppe; Garribba, Eugenio; Rompel, Annette; Crans, Debbie C.Polyoxovanadates (POVs) are a subclass of a larger family of polyanionic group V and VI metal-oxo clus ters that are known as polyoxometalates (POMs). POMs have been found to have antidiabetic, antibacte rial, antiprotozoal, antiviral and anticancer activities, which have sparked interest in their use as bioinorganic drugs. Among POVs, decavanadate ([V10O28] 6 ; V10) is an isopolyoxovanadate recently described to have several medicinal applications. In the present review, recent insights into POVs with emergent anticancer, antimicrobial and antiviral applications are described. Additionally, POVs’ stability and speciation under experimental biological conditions as well as POVs (in particular, V10) in vivo and ex vivo effects are highlighted. Finally, we report the most important 21st century studies of POVs’ effects and/or targets against cancer, bacteria and viruses including: apoptosis, cell cycle arrest, interference with ions transport system, inhibition of mRNA synthesis, cell morphology changes, changes in metabolic pathways, phosphorylase enzyme inhibition and cell signaling, formation of reactive oxygen species, lipid peroxidation, inhibition of viral mRNA polymerase, inhibition of virus binding to the host cell, penetra tion and interaction with virus protein cages.
- The aquaporin-3-inhibiting potential of polyoxotungstatesPublication . Pimpão, Catarina; da Silva, Inês V.; Mósca, Andreia F.; Pinho, Jacinta O.; Gaspar, Maria Manuela; Gumerova, Nadiia I.; Rompel, Annette; Aureliano, Manuel; Soveral, GraçaPolyoxometalates (POMs) are of increasing interest due to their proven anticancer activities. Aquaporins (AQPs) were found to be overexpressed in tumors bringing particular attention to their inhibitors as anticancer drugs. Herein, we report for the first time the ability of polyoxotungstates (POTs), such as of Wells-Dawson P2W18, P2W12, and P2W15, and Preyssler P5W30 structures, to affect aquaporin-3 (AQP3) activity and impair melanoma cell migration. The tested POTs were revealed to inhibit AQP3 function with different effects, with P2W18, P2W12, and P5W30 being the most potent (50% inhibitory concentration (IC50) = 0.8, 2.8, and 3.2 µM), and P2W15 being the weakest (IC50 > 100 µM). The selectivity of P2W18 toward AQP3 was confirmed in yeast cells transformed with human aquaglyceroporins. The effect of P2W12 and P2W18 on melanoma cells that highly express AQP3 revealed an impairment of cell migration between 55% and 65% after 24 h, indicating that the anticancer properties of these compounds may in part be due to the blockage of AQP3-mediated permeability. Altogether, our data revealed that P2W18 strongly affects AQP3 activity and cancer cell growth, unveiling its potential as an anticancer drug against tumors where AQP3 is highly expressed.
- The biological applications of metals and metal complexesPublication . Aureliano, Manuel; Gumerova, Nadiia I.; Rompel, AnnetteOver the course of biological evolution, approximately 25 to 30 elements have been recognized as essential for the proper functioning of biological systems since the emergence of life [...]
- The preyssler-type polyoxotungstate exhibits anti-quorum sensing, antibiofilm, and antiviral activitiesPublication . Faleiro, Maria Leonor; Marques, Ana; Martins, João; Jordão, Luísa; Nogueira, Isabel; Gumerova, Nadiia I.; Rompel, Annette; Aureliano, M.The increase in bacterial resistance to antibiotics has led researchers to find new compounds or find combinations between different compounds with potential antibacterial action and with the ability to prevent the development of antibiotic resistance. Polyoxotungstates (POTs) are inorganic clusters that may fulfill that need, either individually or in combination with antibiotics. Herein, we report the ability of the polyoxotungstates (POTs) with Wells-Dawson P2W18, P2W17, P2W15, and Preyssler P5W30 type structures to differently affect Gram-negative and Gram-positive microorganisms, either susceptible or resistant to antibiotics. The compound P5W30 showed the highest activity against the majority of the tested bacterial strains in comparison with the other tested POTs (P2W15, P2W17 and P2W18) that did not show inhibition zones for the Gram-negative bacteria, A. baumanii I73775, E. coli DSM 1077, E. coli I73194, K. pneumoniae I7092374, and P. aeruginosa C46281). Generally, the results evidenced that Gram-positive bacteria are more susceptible to the POTs tested. The compound P5W30 was the one most active against S. aureus ATCC 6538 and MRSA16, reaching <0.83 mg·mL−1 (100 µM) and 4.96 mg·mL−1 (600 µM), respectively. Moreover, it was verified by NMR spectroscopy that the most promising POT, P5W30, remains intact under all the experimental conditions, after 24 h at 37 ◦C. This prompted us to further evaluate the anti-quorum sensing activity of P5W30 using the biosensor Chromobacterium violaceum CV026, as well as its antibiofilm activity both individually and in combination with the antibiotic cefoxitin against the methicillin-resistant Staphylococcus aureus 16 (MRSA16). P5W30 showed a synergistic antibacterial effect with the antibiotic cefoxitin and chloramphenicol against MRSA16. Moreover, the antibiofilm activity of P5W30 was more pronounced when used individually, in comparison with the combination with the antibioticcefoxitin. Finally, the antiviral activity of P5W30 was tested using the coliphage Qβ, showing a dosedependent response. The maximum inactivation was observed at 750 µM (6.23 mg·mL−1 ). In sum, P5W30 shows anti-quorum sensing and antibiofilm activities besides being a potent antibacterial agent against S. aureus and to exhibit antiviral activities against enteric viruses.
- Unveiling the agonistic properties of Preyssler-type Polyoxotungstates on purinergic P2 receptorsPublication . Poejo, Joana; Gumerova, Nadiia I.; Rompel, Annette; Mata, Ana M.; Aureliano, Manuel; Gutierrez-Merino, CarlosThe Preyssler-type polyoxotungstate ({P5W30}) belongs to the family of polyanionic metal-oxides formed by group V and VI metal ions, such as V, Mo and W, commonly known as polyoxometalates (POMs). POMs have demonstrated inhibitory effect on a significant number of ATP-binding proteins in vitro. Purinergic P2 receptors, widely expressed in eukaryotic cells, contain extracellularly oriented ATP-binding sites and play many biological roles with health implications. In this work, we use the immortalized mouse hippocampal neuronal HT-22 cells in culture to study the effects of {P5W30} on the cytosolic Ca2+ concentration. Changes in cytosolic Ca2+ concentration were monitored using fluorescence microscopy of HT-22 cells loaded with the fluorescent Ca2+ indicator Fluo3. 31P-Nuclear magnetic resonance measurements of {P5W30} indicate its stability in the medium used for cytosolic Ca2+ measurements for over 30 min. The findings reveal that addition of {P5W30} to the extracellular medium induces a sustained increase of the cytosolic Ca2+ concentration within minutes. This Ca2+ increase is triggered by extracellular Ca2+ entry into the cells and is dose-dependent, with a half-of-effect concentration of 0.25 ± 0.05 μM {P5W30}. In addition, after the {P5W30}-induced cytosolic Ca2+ increase, the transient Ca2+ peak induced by extracellular ATP is reduced up to 100% with an apparent half-of-effect concentration of 0.15 ± 0.05 μM {P5W30}. Activation of metabotropic purinergic P2 receptors affords about 80% contribution to the increase of Fluo3 fluorescence elicited by {P5W30} in HT-22 cells, whereas ionotropic receptors contribute, at most, with 20%. These results suggest that {P5W30} could serve as a novel agonist of purinergic P2 receptors.