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Frontiers in Chemistry 2021Nanosized titanium oxide (TiO)-based photocatalysts have exhibited great potential for the degradation of organic contaminants, while their weak absorption of visible...
Preparation and Characterization of Reduced Graphene Oxide /TiO Blended Polyphenylene sulfone Antifouling Composite Membrane With Improved Photocatalytic Degradation Performance.
Nanosized titanium oxide (TiO)-based photocatalysts have exhibited great potential for the degradation of organic contaminants, while their weak absorption of visible light limits the photocatalytic efficiency. Herein, a novel reduced graphene oxide/TiO-polyphenylenesulfone (rGO/TiO-PPSU) hybrid ultrafiltration membrane has been successfully prepared via a non-solvent induced phase-separation method, in which the synergistic coupling between the rGO and TiO could endowed the fabricated membranes with visible-light-driven efficient photocatalytically degradation of organic pollutants and outstanding photocatalytic and antifouling properties. Compared with the PPSU membranes prepared with Graphene oxide and TiO, respectively, the rGO/TiO-PPSU membrane demonstrated significant photodegradation towards phenazopyridine hydrochloride (PhP) solution under ultraviolet light (improved about 71 and 43%) and visible light (improved about 153 and 103%). The permeability and flux recovery rates of the membrane indicated that the high flux of the rGO/TiO-PPSU membrane can be greatly restored after fouling, due to the improved self-cleaning properties under visible light static irradiation. With the properties of high performance of photocatalytic degradation and good self-cleaning ability, the rGO/TiO-PPSU membrane would have great potential in water treatment.
PubMed: 34738005
DOI: 10.3389/fchem.2021.753741 -
Nature Communications Sep 2021Chiral bridged [2,2,1] bicyclic lactones are privileged structural units in pharmaceutics and bioactive nature products. However, the synthetic methods for these...
Chiral bridged [2,2,1] bicyclic lactones are privileged structural units in pharmaceutics and bioactive nature products. However, the synthetic methods for these compounds are rare. Here we report an efficient method for enantioselective construction of bridged [2,2,1] bicyclic lactones bearing a quaternary stereocenter via Rh-catalyzed asymmetric hydroformylation/intramolecular cyclization/pyridium chlorochromate (PCC) oxidation. By employing a hybrid phosphine-phosphite chiral ligand, a series of cyclopent-3-en-1-ols are transformed into corresponding γ-hydroxyl aldehydes with specific syn-selectivity. Then, hemiacetals form in situ and oxidation with PCC in one-pot affords bridged [2,2,1] bicyclic lactones in high yields and excellent enantiomeric excess. Replacing the hydroxyl group by an ester group, cyclopentanecarbaldehydes with a chiral all-carbon quaternary stereocenter in the γ-position can be generated efficiently.
Topics: Aldehydes; Bridged Bicyclo Compounds, Heterocyclic; Cyclization; Cyclopentanes; Formates; Humans; Lactones; Oxidation-Reduction; Phenazopyridine; Phosphines; Phosphites; Stereoisomerism; Water
PubMed: 34489434
DOI: 10.1038/s41467-021-25569-5 -
Frontiers in Pharmacology 2021Phenazopyridine is a widely used drug against urinary tract pain. The compound has also been shown to enhance neural differentiation of pluripotent stem cells. However,...
Phenazopyridine is a widely used drug against urinary tract pain. The compound has also been shown to enhance neural differentiation of pluripotent stem cells. However, its mechanism of action is not understood. Based on its chemical structure, we hypothesized that phenazopyridine could be a kinase inhibitor. Phenazopyridine was investigated in the following experimental systems: 1) activity of kinases in pluripotent stem cells; 2) binding to recombinant kinases, and 3) functional impact on pluripotent stem cells. Upon addition to pluripotent stem cells, phenazopyridine induced changes in kinase activities, particularly involving Mitogen-Activated Protein Kinases, Cyclin-Dependent Kinases, and AKT pathway kinases. To identify the primary targets of phenazopyridine, we screened its interactions with 401 human kinases. Dose-inhibition curves showed that three of these kinases interacted with phenazopyridine with sub-micromolar binding affinities: cyclin-G-associated kinase, and the two phosphatidylinositol kinases PI4KB and PIP4K2C, the latter being known for participating in pain induction. Docking revealed that phenazopyridine forms strong H-bonds with the hinge region of the ATP-binding pocket of these kinases. As previous studies suggested increased autophagy upon inhibition of the phosphatidyl-inositol/AKT pathway, we also investigated the impact of phenazopyridine on this pathway and found an upregulation. In conclusion, our study demonstrates for the first time that phenazopyridine is a kinase inhibitor, impacting notably phosphatidylinositol kinases involved in nociception.
PubMed: 34421588
DOI: 10.3389/fphar.2021.664608 -
The Canadian Veterinary Journal = La... Jul 2021The objective of this study was to describe the clinical findings, medical management, and outcomes of horses with sabulous cystitis, and to describe a high flow bladder...
The objective of this study was to describe the clinical findings, medical management, and outcomes of horses with sabulous cystitis, and to describe a high flow bladder lavage procedure in horses that are standing or under general anesthesia. The medical records of 13 horses diagnosed with sabulous cystitis cystoscopy between 2013 and 2020 were reviewed. Geldings (92%) and Warmbloods (46%) were overrepresented. The most common presenting complaint was urinary incontinence (69%). Complete blood cell count, serum biochemistry profile and urine cytology results were non-specific. Six (46%) horses had various degrees of erosion, ulceration, and hemorrhage of the bladder mucosa. All horses were treated with bladder lavage either with standing sedation ( = 12) or general anesthesia ( = 2), as well as antimicrobials (54%), anti-inflammatory drugs (62%), bethanechol (15%), and phenazopyridine (15%). Most horses (85%) were discharged from the hospital, but only a small percentage (23%) was reported as having no urinary abnormalities on follow-up communication. Key clinical message: Copious bladder lavage with a high flow rate system could mitigate the acute clinical signs and improve the quality of life of horses with sabulous cystitis, but the prognosis for return to previous level of athletic performance and long-term survival is guarded.
Topics: Animals; Cystitis; Horse Diseases; Horses; Male; Quality of Life; Urinary Incontinence
PubMed: 34219784
DOI: No ID Found -
Scientific Reports Jan 2021The present study has focused on the degradation of phenazopyridine (PhP) as an emerging contaminant through catalytic ozonation by novel plasma treated natural limonite...
The present study has focused on the degradation of phenazopyridine (PhP) as an emerging contaminant through catalytic ozonation by novel plasma treated natural limonite (FeOOH·xHO, NL) under argon atmosphere (PTL/Ar). The physical and chemical characteristics of samples were evaluated with different analyses. The obtained results demonstrated higher surface area for PTL/Ar and negligible change in crystal structure, compared to NL. It was found that the synergistic effect between ozone and PTL/Ar nanocatalyst was led to highest PhP degradation efficiency. The kinetic study confirmed the pseudo-first-order reaction for the PhP degradation processes included adsorption, peroxone and ozonation, catalytic ozonation with NL and PTL/Ar. Long term application (6 cycles) confirmed the high stability of the PTL/Ar. Moreover, different organic and inorganic salts as well as the dissolved ozone concentration demonstrated the predominant role of hydroxyl radicals and superoxide radicals in PhP degradation by catalytic Ozonation using PTL/Ar. The main produced intermediates during PhP oxidation by PTL/Ar catalytic ozonation were identified using LC-(+ESI)-MS technique. Finally, the negligible iron leaching, higher mineralization rate, lower electrical energy consumption and excellent catalytic activity of PTL/Ar samples demonstrate the superior application of non-thermal plasma for treatment of NL.
PubMed: 33441829
DOI: 10.1038/s41598-020-80200-9 -
ChemMedChem Apr 2021Rev1 is a protein scaffold of the translesion synthesis (TLS) pathway, which employs low-fidelity DNA polymerases for replication of damaged DNA. The TLS pathway helps...
Rev1 is a protein scaffold of the translesion synthesis (TLS) pathway, which employs low-fidelity DNA polymerases for replication of damaged DNA. The TLS pathway helps cancers tolerate DNA damage induced by genotoxic chemotherapy, and increases mutagenesis in tumors, thus accelerating the onset of chemoresistance. TLS inhibitors have emerged as potential adjuvant drugs to enhance the efficacy of first-line chemotherapy, with the majority of reported inhibitors targeting protein-protein interactions (PPIs) of the Rev1 C-terminal domain (Rev1-CT). We previously identified phenazopyridine (PAP) as a scaffold to disrupt Rev1-CT PPIs with Rev1-interacting regions (RIRs) of TLS polymerases. To explore the structure-activity relationships for this scaffold, we developed a protocol for co-crystallization of compounds that target the RIR binding site on Rev1-CT with a triple Rev1-CT/Rev7 /Rev3-RBM1 complex, and solved an X-ray crystal structure of Rev1-CT bound to the most potent PAP analogue. The structure revealed an unexpected binding pose of the compound and informed changes to the scaffold to improve its affinity for Rev1-CT. We synthesized eight additional PAP derivatives, with modifications to the scaffold driven by the structure, and evaluated their binding to Rev1-CT by microscale thermophoresis (MST). Several second-generation PAP derivatives showed an affinity for Rev1-CT that was improved by over an order of magnitude, thereby validating the structure-based assumptions that went into the compound design.
Topics: Dose-Response Relationship, Drug; Drug Design; Enzyme Inhibitors; Humans; Molecular Structure; Nucleotidyltransferases; Phenazopyridine; Structure-Activity Relationship
PubMed: 33314657
DOI: 10.1002/cmdc.202000893 -
Urology Journal Sep 2020Intravesical BCG (Bacillus Calmette-Guérin) therapy is indicated as an effective treatment for patients with non-muscle-invasive bladder cancer, despite associate with... (Randomized Controlled Trial)
Randomized Controlled Trial
Comparison of the Efficacy of Oxybutynin, Phenazopyridine, Celecoxib, and Placebo in the Treatment of Urinary Tract Symptoms after BCG Therapy in Patients with Bladder Tumors.
PURPOSE
Intravesical BCG (Bacillus Calmette-Guérin) therapy is indicated as an effective treatment for patients with non-muscle-invasive bladder cancer, despite associate with the side effects. In this study, the incidence of BCG therapy adverse effects was compared among three groups of patients who received celecoxib, phenazopyridine, and oxybutynin with placebo.
MATERIALS AND METHODS
The randomized controlled clinical trial was conducted on four groups using the parallel group method. A checklist is used for weekly assessment of urinary symptoms, systemic symptoms of BCG therapy, and adverse drug reactions.
RESULTS
The study included 120 patients, 10 female and 110 male. The mean age 59.65 ± 6.2 years. The results of multivariate analysis show that there is a significant decrease in urinary frequency for patients who received phenazopyridine (95% CI: 0.09, 0.31, OR = 0.17, P <.001) and also celecoxib group (95% CI: 0.10, 0.43, OR = 0.21, P <.001) compared to those in placebo group. Patients in celecoxib group (95% CI: 0.02, 0.07 ,OR = 0.04, P <.001), phenazopyridine (95% CI : 0.07, 0.37,OR=0.16, P <.001) and oxybutynin (95% CI: 0.02, 0.12,OR = 0.05, P <.001) were less likely to have urgency than those in placebo. Moreover, significant decrease was found for dysuria in the three treatment groups in comparison with placebo group.
CONCLUSION
According to the results, celecoxib, phenazopyridine and oxybutynin can effectively decrease the side effects of BCG immunotherapy compared to placebo. Among these three treatments, the most effective and safest treatment option is celecoxib.
Topics: Adjuvants, Immunologic; Administration, Intravesical; Aged; BCG Vaccine; Celecoxib; Female; Humans; Male; Mandelic Acids; Middle Aged; Phenazopyridine; Urinary Bladder Neoplasms; Urinary Tract
PubMed: 32981029
DOI: 10.22037/uj.v16i7.5947 -
Journal of Pain and Symptom Management Apr 2021Dysphagia is a common concern, especially in the last several days of life. Medications are often crushed for ease of administration for individuals with swallowing...
CONTEXT
Dysphagia is a common concern, especially in the last several days of life. Medications are often crushed for ease of administration for individuals with swallowing difficulty.
OBJECTIVES
To assess palatability of commonly used crushed over-the-counter (OTC) medications. A secondary objective is to evaluate pharmacist knowledge and opinions of crushing medications.
METHODS
Pharmacist participants sampled crushed OTC medications and completed presampling and postsampling surveys about crushing medications. Participants were excluded for current smoking or tobacco use, pregnancy, allergy to any study medication or applesauce, or potential drug-drug interaction with study medications. Eight OTC medications were crushed and mixed in applesauce: naproxen, fexofenadine, phenazopyridine, multivitamin, loperamide, famotidine, sennosides, and sennosides-docusate. Participants were blinded to medication samples and control (plain applesauce). Samples were rated from one (least palatable) to five (most palatable). Investigators recorded participants' comments, behaviors, and facial expressions during sampling.
RESULTS
Nineteen volunteers completed the study. Most participants rated three samples as not palatable (score of two or less): fexofenadine, 16 (84%); loperamide, 13 (68%); and sennosides-docusate, 16 (84%). All participants rated famotidine and sennosides palatable. The percentage of participants who would consider palatability in recommendations for crushing medications increased from 47% prestudy to 79% poststudy.
CONCLUSION
Palatability should be considered when recommending crushed medications. Survey responses indicate that pharmacists' opinions of crushed medications changed after this palatability experiment. Clinicians should evaluate the appropriateness of all medications when dysphagia is a concern and deprescribe medications when appropriate to reduce burden for patients and caregivers.
Topics: Deglutition Disorders; Humans; Surveys and Questionnaires
PubMed: 32976943
DOI: 10.1016/j.jpainsymman.2020.09.020 -
Pharmaceutical Research Nov 2019The intracellular fraction of unbound compound (f) is an important parameter for accurate prediction of drug binding to intracellular targets. f is the result of a...
PURPOSE
The intracellular fraction of unbound compound (f) is an important parameter for accurate prediction of drug binding to intracellular targets. f is the result of a passive distribution process of drug molecules partitioning into cellular structures. Initial observations in our laboratory showed an up to 10-fold difference in the f of a given drug for different cell types. We hypothesized that these differences could be explained by the phospholipid (PL) composition of the cells, since the PL cell membrane is the major sink of unspecific drug binding. Therefore, we determined the f of 19 drugs in cell types of different origin.
METHOD
The cells were characterized for their total PL content and we used mass spectrometric PL profiling to delineate the impact of each of the four major cellular PL subspecies: phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS) and phosphatidylinositol (PI). The cell-based experiments were compared to cell-free experiments that used beads covered by PL bilayers consisting of the most abundant PL subspecies.
RESULTS
PC was found to give the largest contribution to the drug binding. Improved correlations between the cell-based and cell-free assays were obtained when affinities to all four major PL subspecies were considered. Together, our data indicate that f is influenced by PL composition of cells.
CONCLUSION
We conclude that cellular PL composition varies between cell types and that cell-specific mixtures of PLs can replace cellular assays for determination of f as a rapid, small-scale assay covering a broad dynamic range. Graphical Abstract.
Topics: Biological Availability; Biological Transport; Caffeine; Cell Line; Cell Membrane; Computer Simulation; Cytoplasm; Drug Interactions; Humans; Models, Biological; Phenazopyridine; Phospholipids
PubMed: 31701258
DOI: 10.1007/s11095-019-2717-1 -
ChemMedChem Sep 2019Translesion synthesis (TLS) has emerged as a mechanism through which several forms of cancer develop acquired resistance to first-line genotoxic chemotherapies by...
Translesion synthesis (TLS) has emerged as a mechanism through which several forms of cancer develop acquired resistance to first-line genotoxic chemotherapies by allowing replication to continue in the presence of damaged DNA. Small molecules that inhibit TLS hold promise as a novel class of anticancer agents that can serve to enhance the efficacy of these front-line therapies. We previously used a structure-based rational design approach to identify the phenazopyridine scaffold as an inhibitor of TLS that functions by disrupting the protein-protein interaction (PPI) between the C-terminal domain of the TLS DNA polymerase Rev1 (Rev1-CT) and the Rev1 interacting regions (RIR) of other TLS DNA polymerases. To continue the identification of small molecules that disrupt the Rev1-CT/RIR PPI, we generated a pharmacophore model based on the phenazopyridine scaffold and used it in a structure-based virtual screen. In vitro analysis of promising hits identified several new chemotypes with the ability to disrupt this key TLS PPI. In addition, several of these compounds were found to enhance the efficacy of cisplatin in cultured cells, highlighting their anti-TLS potential.
Topics: Animals; Azo Compounds; DNA-Directed DNA Polymerase; Drug Evaluation, Preclinical; Mice; Molecular Docking Simulation; Molecular Dynamics Simulation; Nucleotidyltransferases; Protein Binding; Protein Domains; Pyridines
PubMed: 31361935
DOI: 10.1002/cmdc.201900307