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Journal of Chromatography. A Dec 2020The capability of liquid chromatography with microemulsions (MEs) as mobile phases was studied for the analysis of four parabens (butylparaben, ethylparaben,...
The capability of liquid chromatography with microemulsions (MEs) as mobile phases was studied for the analysis of four parabens (butylparaben, ethylparaben, methylparaben, and propylparaben) and seven β-adrenoceptor antagonists (acebutolol, atenolol, carteolol, metoprolol, oxprenolol, propranolol, and timolol). MEs were formed by mixing aqueous solutions of the anionic surfactant sodium dodecyl sulphate, the alcohol 1-butanol that played the role of co-surfactant, and octane as oil. In order to guarantee the formation of stable MEs, a preliminary study was carried out to determine the appropriate ranges of concentrations of the three components. For this purpose, mixtures of variable composition were prepared, and the possible separation of two phases (formation of an emulsion) was visually detected. The advantage offered by the addition of octane to micellar mobile phases, inside the concentration range that allows the formation of stable MEs, was evaluated by comparing the retention behaviour, peak profile and resolution of mixtures of the probe compounds, in the presence and absence of octane. The final aim of this work was the proposal of a mathematical equation to model the retention behaviour in microemulsion liquid chromatography. The derived global model that considered the three factors (surfactant, alcohol and oil) allowed the prediction of retention times at diverse mobile phase compositions with satisfactory accuracy (in the 1.1‒2.5% range). The behaviour was compared with that found with mobile phases without octane. The model also yielded information about the retention mechanism and revealed that octane, when inserted inside the micelle, modifies the interaction between solutes and micelles.
Topics: Butanols; Chromatography, Liquid; Emulsions; Micelles; Models, Chemical; Parabens; Sodium Dodecyl Sulfate; Surface-Active Agents; Water
PubMed: 33166895
DOI: 10.1016/j.chroma.2020.461651 -
Chemosphere Aug 2023Progress in excogitation suitable strategies for monitoring chemical compounds in wastewater is an essential step for further research into the occurrence, impact, and...
Progress in excogitation suitable strategies for monitoring chemical compounds in wastewater is an essential step for further research into the occurrence, impact, and fate of the pollutants in the aquatic environment. At present, it is desirable to advance and use economical, environmentally friendly and non-labour intensive methods of environmental analysis. In this study, carbon nanotubes (CNTs) were successfully applied, regenerated, and reused as a sorbent in passive samplers for monitoring contaminants in treated and untreated wastewater at three wastewater treatment plants (WWTPs) located in different urbanization areas in northern Poland. Three cycles of chemical and thermal regeneration of used sorbents were performed. It was shown that it is possible to regenerate CNTs a minimum of three times and reuse them in passive samplers while maintaining the desired sorption properties. The obtained results confirm that the CNTs are perfectly in line with the main principles of green chemistry and sustainability. Carbamazepine, ketoprofen, naproxen, diclofenac, p-nitrophenol, atenolol, acebutolol, metoprolol, sulfapyridine and sulfamethoxazole were detected in each of the WWTPs, both in treated and untreated wastewater. The obtained data drastically show the inefficiency of the removal of contaminants by conventional WWTPs. More importantly, the results even indicate negative contaminant removal in most cases, i.e. higher concentrations (up to 863%) of these substances in the effluent compared to the influent.
Topics: Wastewater; Nanotubes, Carbon; Environmental Monitoring; Water Pollutants, Chemical; Carbamazepine
PubMed: 37149101
DOI: 10.1016/j.chemosphere.2023.138855 -
Journal of Mass Spectrometry : JMS Dec 2023Beta blockers are a class of drugs commonly used to treat heart-related diseases; they are also regulated under the World Anti-Doping Agency. Tandem mass spectrometry is...
Beta blockers are a class of drugs commonly used to treat heart-related diseases; they are also regulated under the World Anti-Doping Agency. Tandem mass spectrometry is often used in the pharmaceutical industry, clinical analysis laboratory, and antidoping laboratory for detection and characterization of drugs and their metabolites. A deeper chemical understanding of dissociation pathways may eventually lead to an improved ability to predict tandem mass spectra of compounds based strictly on their chemical structure (or vice versa), which is especially important for characterization of unknowns such as emerging designer drugs or novel metabolites. In addition to providing insights into dissociation pathways, the use of energy-resolved breakdown curves can produce improved selectivity and lend insights into optimal fragmentation conditions for liquid chromatography-tandem mass spectrometry LC-MS/MS workflows. Here, we perform energy-resolved collision cell and multistage ion trap collision-induced dissociation-mass spectrometry (CID-MS) experiments, along with complementary density functional theory calculations, on five beta blockers (acebutolol, atenolol, bisoprolol, carteolol, and labetalol), to better understand the details of the pathways giving rise to the observed MS/MS patterns. Results from this work are contextualized within previously reported literature on these compounds. New insights into the formation of the characteristic product ion m/z 116 and the pathway leading to characteristic loss of 77 u are highlighted. We also present comparisons of breakdown curves obtained via qToF, quadrupole ion trap, and in-source CID, allowing for differences between the data to be noted and providing a step toward allowing for improved selectivity of breakdown curves to be realized on simple instruments such as single quadrupoles or ion traps.
Topics: Tandem Mass Spectrometry; Bisoprolol; Carteolol; Labetalol; Chromatography, Liquid; Acebutolol; Atenolol
PubMed: 37990768
DOI: 10.1002/jms.4985 -
Molecules (Basel, Switzerland) Nov 2020In this work, one of the most prevalent polypharmacology drug-drug interaction events that occurs between two widely used beta-blocker drugs-i.e., acebutolol and...
In this work, one of the most prevalent polypharmacology drug-drug interaction events that occurs between two widely used beta-blocker drugs-i.e., acebutolol and propranolol-with the most abundant blood plasma fibrinogen protein was evaluated. Towards that end, molecular docking and Density Functional Theory (DFT) calculations were used as complementary tools. A fibrinogen crystallographic validation for the three best ranked binding-sites shows 100% of conformationally favored residues with total absence of restricted flexibility. From those three sites, results on both the binding-site druggability and ligand transport analysis-based free energy trajectories pointed out the most preferred biophysical environment site for drug-drug interactions. Furthermore, the total affinity for the stabilization of the drug-drug complexes was mostly influenced by steric energy contributions, based mainly on multiple hydrophobic contacts with critical residues (THR22: P and SER50: Q) in such best-ranked site. Additionally, the DFT calculations revealed that the beta-blocker drug-drug complexes have a spontaneous thermodynamic stabilization following the same affinity order obtained in the docking simulations, without covalent-bond formation between both interacting beta-blockers in the best-ranked site. Lastly, experimental ultrasound density and velocity measurements were performed and allowed us to validate and corroborate the computational obtained results.
Topics: Adrenergic beta-Antagonists; Binding Sites; Density Functional Theory; Drug Interactions; Fibrinogen; Ligands; Molecular Conformation; Molecular Docking Simulation; Reproducibility of Results; Thermodynamics
PubMed: 33228181
DOI: 10.3390/molecules25225425 -
European Journal of Nuclear Medicine... Nov 2019Targeting fibroblast activation protein (FAP) is a new diagnostic approach allowing the visualization of tumor stroma. Here, we applied FAP-specific PET imaging to...
PURPOSE
Targeting fibroblast activation protein (FAP) is a new diagnostic approach allowing the visualization of tumor stroma. Here, we applied FAP-specific PET imaging to gliomas. We analyzed the target affinity and specificity of two FAP ligands (FAPI-02 and FAPI-04) in vitro, and the pharmacokinetics and biodistribution in mice in vivo. Clinically, we used Ga-labeled FAPI-02/04 for PET imaging in 18 glioma patients (five IDH-mutant gliomas, 13 IDH-wildtype glioblastomas).
METHODS
For binding studies with Lu-radiolabeled FAPI-02/04, we used the glioblastoma cell line U87MG, FAP-transfected fibrosarcoma cells, and CD26-transfected human embryonic kidney cells. For pharmacokinetic and biodistribution studies, U87MG-xenografted mice were injected with Ga-labeled compounds followed by small-animal PET imaging and Lu-labeled FAPI-02/04, respectively. Clinical PET/CT scans were performed 30 min post intravenous administration of Ga-FAPI-02/04. PET and MRI scans were co-registrated. Immunohistochemistry was done on 14 gliomas using a FAP-specific antibody.
RESULTS
FAPI-02 and FAPI-04 showed high binding specificity to FAP. FAPI-04 demonstrated higher tumor accumulation and delayed elimination compared with FAPI-02 in preclinical studies. IDH-wildtype glioblastomas and grade III/IV, but not grade II, IDH-mutant gliomas showed elevated tracer uptake. In glioblastomas, we observed spots with increased uptake in projection on contrast-enhancing areas. Immunohistochemistry showed FAP-positive cells with mainly elongated cell bodies and perivascular FAP-positive cells in glioblastomas and an anaplastic IDH-mutant astrocytoma.
CONCLUSIONS
Using FAP-specific PET imaging, increased tracer uptake in IDH-wildtype glioblastomas and high-grade IDH-mutant astrocytomas, but not in diffuse astrocytomas, may allow non-invasive distinction between low-grade IDH-mutant and high-grade gliomas. Therefore, FAP-specific imaging in gliomas may be useful for follow-up studies although further clinical evaluation is required.
Topics: Acebutolol; Adult; Animals; Biological Transport; Brain Neoplasms; Cell Line, Tumor; Endopeptidases; Female; Gelatinases; Glioblastoma; Humans; Isocitrate Dehydrogenase; Ligands; Membrane Proteins; Mice; Middle Aged; Mutation; Naphthols; Neoplasm Grading; Positron Emission Tomography Computed Tomography; Radioactive Tracers; Serine Endopeptidases; Triazines; Young Adult
PubMed: 31388723
DOI: 10.1007/s00259-019-04444-y -
Mikrochimica Acta Mar 2021Molybdenum disulfide (MoS) surface functionalization was performed with a catechol-containing polymer sodium alginate (SA) and dopamine (DA) through simultaneous MoS...
Molybdenum disulfide (MoS) surface functionalization was performed with a catechol-containing polymer sodium alginate (SA) and dopamine (DA) through simultaneous MoS exfoliation and self-polymerization of DA. The MoS/SA-PDA nanocomposite was characterized using spectroscopic, microscopic, and electroanalytical techniques to evaluate its electrocatalytic performance. The electrocatalytic behavior of the MoS/SA-PDA nanocomposite modified electrode for the detection of acebutolol (ACE), a cardio-selective β-blocker drug was explored through cyclic voltammetric and differential pulse voltammetric techniques. The influence of scan rate, concentration, and pH value on the oxidation peak current of ACE was investigated to optimize the deducting condition. The electrochemical activity of the MoS/SA-PDA nanocomposite electrode was attributed to the existence of reactive functional groups being contributed from SA, PDA, and MoS exhibiting a synergic effect. The MoS/SA-PDA nanocomposite modified electrode exhibits admirable electrocatalytic activity with a wide linear response range (0.009 to 520 μM), low detection limit (5 nM), and high sensitivity (0.354 μA μM cm) also in the presence of similar (potentially interfering) compounds. The fabricated MoS/SA-PDA nanocomposite modified electrode can be useful for the detection of ACE in pharmaceutical analysis.
Topics: Acebutolol; Adrenergic beta-1 Receptor Antagonists; Alginates; Biosensing Techniques; Disulfides; Electrochemical Techniques; Electrodes; Humans; Indoles; Limit of Detection; Molybdenum; Nanocomposites; Oxidation-Reduction; Polymers; Reproducibility of Results
PubMed: 33646401
DOI: 10.1007/s00604-021-04717-0 -
Current Computer-aided Drug Design 2021The aim of the study was to develop new SIRT1 activator compounds, for this aim, we used virtual screening and molecular dynamics methods, which have been important...
AIM
The aim of the study was to develop new SIRT1 activator compounds, for this aim, we used virtual screening and molecular dynamics methods, which have been important tools for new hit compound searches.
BACKGROUND
Recently, with the progress of computing technology, it has been possible to obtain higher efficiency and lower costs for drug discovery. With in silico research and drug design, there is a reduction in time-consuming and expensive experimental work. An NAD+ dependent histone deacetylase enzyme, Sirtuin 1 (SIRT1), is involved in a variety of human disorders such as type II diabetes, cancer, obesity, and aging. Activation of SIRT1 could be useful for longevity and treating metabolic disorders.
OBJECTIVE
We used computational methods to develop new SIRT1 activator compounds.
METHODS
Firstly, virtual screening studies on the human SIRT1 enzyme were carried out. We used approximately 150.000 commercially available compounds from the Zinc database, which include FDA-approved drugs. According to virtual screening results, we selected seven potent activators. Then we compared these hit compounds with known activators by using docking methods. One of these hit compounds, acebutolol, is an FDA-approved drug, and was selected for additional studies using molecular dynamics simulations.
RESULTS
Seven hit compounds were identified with database screening. Each showed strong interactions with SIRT1, and acebutolol formed H-bonds with the important active site residues, Asn226 and/or Glu230 during the dynamics simulation.
CONCLUSION
Based on our in silico studies, the seven most promising compounds, especially acebutolol, showed promising SIRT1 activator potency. The results may be used to design new selective and more potent SIRT1 activator drugs.
Topics: Acebutolol; Age Factors; Aging; Drug Design; Drug Discovery; Enzyme Activators; Humans; Longevity; Molecular Docking Simulation; Molecular Dynamics Simulation; Sirtuin 1
PubMed: 32321406
DOI: 10.2174/1573409916666200422074441 -
International Journal of Legal Medicine Jan 2020The published version of this article unfortunately contained a mistake. In Figure 1 on the molecular network of acebutololol, two molecular structures are not displayed...
The published version of this article unfortunately contained a mistake. In Figure 1 on the molecular network of acebutololol, two molecular structures are not displayed ("acebutolol glucuronide "and "impurity J"). The Figure is corrected here.
PubMed: 31127372
DOI: 10.1007/s00414-019-02073-6 -
Arhiv Za Higijenu Rada I Toksikologiju Mar 2020Beta-blockers are chiral compounds with enantiomers that have different bioactivity, which means that while one is active, the other can be inactive or even harmful. Due...
Beta-blockers are chiral compounds with enantiomers that have different bioactivity, which means that while one is active, the other can be inactive or even harmful. Due to their high consumption and incomplete degradation in waste water, they may reach surface waters and affect aquatic organisms. To address this issue we developed a chromatographic method suitable for determining beta-blocker enantiomers in surface waters. It was tested on five beta-blockers (acebutolol, atenolol, bisoprolol, labetalol and metoprolol) and validated on bisoprolol enantiomers. Good enantioseparation of all analysed beta-blockers was achieved on the Chirobiotic V column with the mobile phase composed of methanol/acetic acid/triethylamine (100/0.20/0.15 v/v/v) at a flow rate of 0.5 mL/min and column temperature of 45 °C. Method proved to be linear in the concentration range from 0.075 µg/mL to 5 µg/mL, and showed good recovery. The limits of bisoprolol enantiomer detection were 0.025 µg/mL and 0.026 µg/mL and of quantification 0.075 µg/mL and 0.075 µg/mL. Despite its limitations, it seems to be a promising method for bisoprolol enantiomer analysis in surface water samples. Further research could focus on waste water analysis, where enantiomer concentrations may be high. Furthermore, transferring the method to a more sensitive one such as liquid chromatography coupled with tandem mass spectrometry and using ammonium acetate as the mobile phase additive instead of acetic acid and triethylamine would perhaps yield much lower limits of detection and quantification.
Topics: Acebutolol; Adrenergic beta-Antagonists; Atenolol; Bisoprolol; Chromatography, High Pressure Liquid; Labetalol; Metoprolol; Water
PubMed: 32597137
DOI: 10.2478/aiht-2020-71-3318 -
Journal of Hazardous Materials Feb 2022The excessive cost, unsustainability or complex production of new highly selective electrocatalysts for HO production, especially noble-metal-based ones, is prohibitive...
The excessive cost, unsustainability or complex production of new highly selective electrocatalysts for HO production, especially noble-metal-based ones, is prohibitive in the water treatment sector. To solve this conundrum, biomass-derived carbons with adequate textural properties were synthesized via agarose double-step pyrolysis followed by steam activation. A longer steam treatment enhanced the graphitization and porosity, even surpassing commercial carbon black. Steam treatment for 20 min yielded the greatest surface area (1248 m g), enhanced the mesopore/micropore volume distribution and increased the activity (E = 0.609 V) and yield of HO (40%) as determined by RRDE. The upgraded textural properties had very positive impact on the ability of the corresponding gas-diffusion electrodes (GDEs) to accumulate HO, reaching Faradaic current efficiencies of ~95% at 30 min. Acidic solutions of β-blocker acebutolol were treated by photoelectro-Fenton (PEF) process in synthetic media with and without chloride. In urban wastewater, total drug disappearance was reached at 60 min with almost 50% mineralization after 360 min at only 10 mA cm. Up to 14 degradation products were identified in the Cl-containing medium.
Topics: Acebutolol; Chlorides; Electrodes; Hydrogen Peroxide; Iron; Oxidation-Reduction; Sepharose; Water Pollutants, Chemical
PubMed: 34479080
DOI: 10.1016/j.jhazmat.2021.127005