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Journal of Biological Inorganic... Mar 2019Three iridium(III) polypyridyl complexes [Ir(ppy)(PYTA)](PF) (1) (ppy = 2-phenylpyridine), [Ir(bzq)(PYTA)](PF) (2) (bzq = benzo[h]quinolone) and...
Three iridium(III) polypyridyl complexes [Ir(ppy)(PYTA)](PF) (1) (ppy = 2-phenylpyridine), [Ir(bzq)(PYTA)](PF) (2) (bzq = benzo[h]quinolone) and [Ir(piq)(PYTA)](PF) (3) (piq = 1-phenylisoquinoline, PYTA = 2,4-diamino-6-(2'-pyridyl)-1,3,5-triazine) were synthesized and characterized by elemental analysis, IR, H NMR and C NMR. The cytotoxic activity of the complexes toward cancer SGC-7901, Eca-109, A549, HeLa, HepG2, BEL-7402 and normal LO2 cell lines was investigated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Complex 3 shows the most effective on inhibiting the above cell growth among these complexes. The complexes locate at the lysosomes and mitochondria. AO/EB, Annex V and PI and comet assays indicate that the complexes can induce apoptosis in SGC-7901 cells. Intracellular ROS and mitochondrial membrane potential were examined under fluorescence microscopy. The results demonstrate that the complexes increase the intracellular ROS levels and induce a decrease in the mitochondrial membrane potential. The complexes can enhance intracellular Ca concentration and cause a release of cytochrome c. The autophagy was studied using MDC staining and western blot. Complexes 1-3 can effectively inhibit the cell invasion with a concentration-dependent manner. Additionally, the complexes target tubules and inhibit the polymerization of tubules. The antimicrobial activity of the complexes against S. aureus, E. coli, Salmonella and L. monocytogenes was explored. The mechanism shows that the complexes induce apoptosis in SGC-7901 cells through ROS-mediated lysosomal-mitochondrial, targeting tubules and damage DNA pathways. Three iridium(III) complexes [Ir(N-C)(PYTA)](PF) (N-C = ppy, 1; bzq, 2; piq, 3) were synthesized and characterized. The anticancer activity of the complexes against SGC-7901 cells was studied by apoptosis, comet assay, autophagy, ROS, mitochondrial membrane potential, intracellular Ca levels, release of cytochrome c, tubules and western blot analysis. The antibacterial activity in vitro was also assayed.
Topics: Anti-Bacterial Agents; Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Cell Proliferation; Cell Survival; Coordination Complexes; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Escherichia coli; Humans; Iridium; Listeria monocytogenes; Microbial Sensitivity Tests; Molecular Structure; Phenazopyridine; Salmonella; Staphylococcus aureus; Structure-Activity Relationship
PubMed: 30564887
DOI: 10.1007/s00775-018-1635-8 -
Journal of Chemical Information and... Nov 2018Translesion synthesis (TLS) is a mechanism of replication past damaged DNA through which multiple forms of human cancer survive and acquire resistance to first-line...
Translesion synthesis (TLS) is a mechanism of replication past damaged DNA through which multiple forms of human cancer survive and acquire resistance to first-line genotoxic chemotherapies. As such, TLS is emerging as a promising target for the development of a new class of anticancer agents. The C-terminal domain of the DNA polymerase Rev1 (Rev1-CT) mediates assembly of the functional TLS complex through protein-protein interactions (PPIs) with Rev1 interacting regions (RIRs) of several other TLS DNA polymerases. Utilizing structural knowledge of the Rev1-CT/RIR interface, we have identified the phenazopyridine scaffold as an inhibitor of this essential TLS PPI. We demonstrate direct binding of this scaffold to Rev1-CT, and the synthesis and evaluation of a small series of analogues have provided important structure-activity relationships for further development of this scaffold. Furthermore, we utilized the umbrella sampling method to predict the free energy of binding to Rev1-CT for each of our analogues. Binding energies calculated through umbrella sampling correlated well with experimentally determined IC values, validating this computational tool as a viable approach to predict the biological activity for inhibitors of the Rev1-CT/RIR PPI.
Topics: Antineoplastic Agents; DNA Damage; DNA Repair; Drug Discovery; Humans; Molecular Docking Simulation; Molecular Dynamics Simulation; Neoplasms; Nuclear Proteins; Nucleotidyltransferases; Phenazopyridine; Protein Interaction Maps; Small Molecule Libraries; Thermodynamics
PubMed: 30289707
DOI: 10.1021/acs.jcim.8b00535 -
Clinical Case Reports Jun 2018Hydroxocobalamin causes reddish discoloration of the urine, mimicking hematuria. Clinicians should be aware of this common side effect of the rarely used drug to prevent...
Hydroxocobalamin causes reddish discoloration of the urine, mimicking hematuria. Clinicians should be aware of this common side effect of the rarely used drug to prevent unnecessary consultations and work-up. Additional benign causes of red urine include foods such as beets, rhubarb, and medications such as rifampin, phenazopyridine.
PubMed: 29881591
DOI: 10.1002/ccr3.1514 -
Analytical Chemistry Jul 2018A design of electromembrane extraction (EME) as a lab on-a-chip device was proposed for the extraction and determination of phenazopyridine as the model analyte. The...
A design of electromembrane extraction (EME) as a lab on-a-chip device was proposed for the extraction and determination of phenazopyridine as the model analyte. The extraction procedure was accomplished by coupling EME and packing a sorbent. The analyte was extracted under the applied electrical field across a membrane sheet impregnated by nitrophenyl octylether (NPOE) into an acceptor phase. It was followed by the absorption of the analyte on strong cation exchanger as a sorbent. The designed chip contained separate spiral channels for donor and acceptor phases featuring embedded platinum electrodes to enhance extraction efficiency. The selected donor and acceptor phases were 0 mM HCl and 100 mM HCl, respectively. The on-chip electromembrane extraction was carried out under the voltage level of 70 V for 50 min. The analysis was carried out by two modes of a simple red-green-blue (RGB) image analysis tool and a conventional HPLC-UV system. After the absorption of the analyte on the solid phase, its color changed and a digital picture of the sorbent was taken for the RGB analysis. The effective parameters on the performance of the chip device, comprising the EME and solid phase microextraction steps, were distinguished and optimized. The accumulation of the analyte on the solid phase showed excellent sensitivity and a limit of detection (LOD) lower than 1.0 μg L achieved by an image analysis using a smartphone. This device also offered acceptable intra- and interassay RSD% (<10%). The calibration curves were linear within the range of 10-1000 μg L and 30-1000 μg L ( r > 0.9969) for HPLC-UV and RGB analysis, respectively. To investigate the applicability of the method in complicated matrixes, urine samples of patients being treated with phenazopyridine were analyzed.
Topics: Adult; Cation Exchange Resins; Chromatography, High Pressure Liquid; Electricity; Electrochemical Techniques; Electrodes; Equipment Design; Female; Humans; Lab-On-A-Chip Devices; Membranes, Artificial; Phenazopyridine; Solid Phase Microextraction; Spectrophotometry, Ultraviolet; Young Adult
PubMed: 29847097
DOI: 10.1021/acs.analchem.8b01224 -
Environmental Technology Sep 2019Photocatalytic degradation of waste pharmaceutics, with solar radiation, is described here as a feasible method to purify pre-contaminated soils. Phenazopyridine has...
Photocatalytic degradation of waste pharmaceutics, with solar radiation, is described here as a feasible method to purify pre-contaminated soils. Phenazopyridine has been used as a model soil contaminant. Two different nano-size powders have been first examined as catalysts, namely commercial TiO (anatase) and commercial ZnO. As the ZnO showed higher catalytic efficiency, the study was then focused on it. The commercial ZnO powder was then compared with lab-prepared ZnO powder, and the latter shows relatively higher efficiency. The ZnO was used in two different ways. In one way, dry ZnO catalyst powder was spread onto the soil, while in the other way the ZnO was sprayed onto the soil surface by a wet spray method. The spray technique shows slightly higher efficiency, in addition to being easier to apply at future large scale. Depending on conditions and type of photocatalyst used, up to 90% contaminant removal can be achieved in 30 min. In case of photocatalysis experiments, the reacted contaminant molecules undergo complete degradation with no detectable side reaction organic products. Possible evaporation or escape of organic contaminant, or other possibly resulting organics, is ruled out by a series of control experiments. Photodegradation process takes place only at the catalytic sites on the soil surface, where contaminant molecules that diffuse from the soil bulk are completely degraded. Other useful organisms inside the soil are not affected as they are kept away from catalyst sites. A plausible mechanism is proposed for the degradation process.
Topics: Catalysis; Phenazopyridine; Photolysis; Soil; Sunlight; Zinc Oxide
PubMed: 29600741
DOI: 10.1080/09593330.2018.1459873 -
Urology May 2018To identify difficult to see ureteral orifices (UOs), urologists need a method to stain the urine. Phenazopyridine, a urinary analgesic which discolors the urine orange,...
OBJECTIVE
To identify difficult to see ureteral orifices (UOs), urologists need a method to stain the urine. Phenazopyridine, a urinary analgesic which discolors the urine orange, can be administered orally preoperatively. We evaluated the usefulness of phenazopyridine in identifying the UOs and optimal timing of administration.
METHODS
Adult patients undergoing endoscopic procedures at the Stratton VA were prospectively enrolled. Preoperative metabolic panels were reviewed. Exclusion criteria were renal insufficiency (creatinine clearance <50 mL/min), severe hepatitis or severe liver disease, glucose-6-phosphate dehydrogenase deficiency, previous hypersensitivity to phenazopyridine, or pregnancy. In phase 1, patients undergoing office flexible cystoscopy were administered 200 mg phenazopyridine the morning of the procedure. Because of the robust orange color of the urine, phase 2 was implemented. In phase 2, patients undergoing rigid cystoscopy in the operating room took 200 mg phenazopyridine at 7 PM the night before surgery. Upon entry into the bladder, UOs were identified and urine color was graded (0 = no dye, 1 = weak, 2 = moderate, and 3 = strong). Patients were assessed postoperatively for side effects.
RESULTS
Five patients were included in phase 1. The mean time from medication to cystoscopy was 153 minutes (range 17-304 minutes). One-third of patients had excretion of grade 3 orange urine that obscured inspection of the bladder mucosa. The study design was adjusted and we transitioned to phase 2. Twenty-three patients were enrolled in phase 2. The mean time from phenazopyridine dose to cystoscopy was 14 hours (range 13-17 hours). Seventy-three percent of patients had grade 2 efflux from the UOs.
CONCLUSION
Phenazopyridine can successfully identify UOs and can be administered as early as the evening before the procedure.
Topics: Aged; Aged, 80 and over; Color; Cystoscopy; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Phenazopyridine; Ureter; Urine
PubMed: 29501712
DOI: 10.1016/j.urology.2018.02.023 -
Female Pelvic Medicine & Reconstructive... 2018To determine the effect of preoperative oral phenazopyridine on postoperative voiding dysfunction in women undergoing a retropubic midurethral sling. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To determine the effect of preoperative oral phenazopyridine on postoperative voiding dysfunction in women undergoing a retropubic midurethral sling.
METHODS
A single-institution randomized clinical trial was performed from September 2015 to March 2017, comparing 200 mg of oral phenazopyridine versus no phenazopyridine in patients undergoing a retropubic midurethral sling under general anesthesia with no concomitant procedures. A power calculation indicated that we required at least 40 subjects per arm. Preoperative demographics, intraoperative medications, blood loss, and complications were recorded. A standardized voiding trial was performed before discharge. Voiding dysfunction was determined by the proportion of subjects who failed a postoperative voiding trial. Pain scores were obtained before and 2 to 3 hours after the surgical procedure. Patient characteristics and surgical data were compared using χ, Fisher exact test, or Wilcoxon rank sum test.
RESULTS
Ninety-two subjects were enrolled in the study. Three patients cancelled their surgery and 1 had an intraoperative urethral injury, leaving 88 patients for the final analysis (44 per arm). Patient demographics showed no differences between groups. Phenazopyridine did not reduce the proportion of patients who failed the voiding trial (27%) compared with subjects who did not receive the medication (21%) (P = 0.453). Postoperative visual analog pain scores were higher in those not receiving phenazopyridine (1.76 vs 1.21, P = 0.046), but after adjusting for the difference in preoperative and postoperative pain scores, the groups showed no difference (P = 0.087).
CONCLUSIONS
Our prospective trial shows that phenazopyridine has no effect on short-term postoperative voiding dysfunction. This condition appears to be multifactorial, and further research is needed.
Topics: Administration, Oral; Anesthesia, General; Anesthetics, Local; Body Mass Index; Female; Humans; Middle Aged; Phenazopyridine; Postoperative Complications; Preoperative Care; Prospective Studies; Suburethral Slings; Treatment Outcome; Urinary Incontinence, Stress; Urinary Retention
PubMed: 29474280
DOI: 10.1097/SPV.0000000000000497 -
Female Pelvic Medicine & Reconstructive... 2019The aims of this study were to determine the efficacy of phenazopyridine when used intraoperatively to assess ureteral patency and to investigate factors that may...
OBJECTIVES
The aims of this study were to determine the efficacy of phenazopyridine when used intraoperatively to assess ureteral patency and to investigate factors that may influence its efficacy.
METHODS
This is a retrospective chart review performed at the Olive View-UCLA Medical Center, a Los Angeles County teaching hospital, from January 2014 through July 2016. Patients undergoing cystoscopy at the time of gynecologic surgery were identified via department case logs. All women receiving preoperative oral phenazopyridine were included. If ureteral flow was unable to be visualized with phenazopyridine alone, the medication was deemed ineffective, and sodium fluorescein was given intraoperatively. Patients were divided into a phenazopyridine effective or phenazopyridine ineffective group. Patient demographics, renal function, intraoperative fluids and urine output, estimated blood loss, timing and dose of medication administration, and complications were gathered from the chart and compared between groups using Fisher exact test, 2-sample t test, Wilcoxon test, and logistic regression for multivariable analysis. P < 0.05 was determined to be significant.
RESULTS
Preoperative phenazopyridine was effective in 190 (91.8%) of 207 patients. It was ineffective in 17 patients who then required intraoperative sodium fluorescein. The group in which phenazopyridine was effective was more likely to have been given a 200-mg (vs 100-mg) dose (P = 0.02) and had lower intraoperative urine output (median, 450 vs 800 mL; P = 0.002).
CONCLUSIONS
Preoperative oral phenazopyridine is effective in more than 90% of cases to detect during gynecologic surgery. A higher phenazopyridine dose and lower intraoperative urine output were associated with increased efficacy.
Topics: Administration, Oral; Adult; Aged; Coloring Agents; Cystoscopy; Female; Fluorescein; Gynecologic Surgical Procedures; Humans; Intraoperative Complications; Intraoperative Period; Middle Aged; Phenazopyridine; Preoperative Period; Retrospective Studies; Surgical Wound; Ureter; Urine
PubMed: 29300258
DOI: 10.1097/SPV.0000000000000540 -
Canadian Urological Association Journal... Jan 2018We sought to determine if patients' perceptions of success or failure of interstitial cystitis/bladder pain syndrome (IC/BPS) therapies proposed in treatment guidelines...
INTRODUCTION
We sought to determine if patients' perceptions of success or failure of interstitial cystitis/bladder pain syndrome (IC/BPS) therapies proposed in treatment guidelines align with the evidence from available clinical trial treatment data.
METHODS
A total of 1628 adult females with a self-reported diagnosis of IC completed a web-based survey in which patients described their perceived outcomes with the therapies they were exposed to. Previously published literature, used in part to develop IC/BPS guidelines, provided the clinical trial data outcomes. Patient-reported outcomes were compared to available clinical trial outcomes and published treatment guidelines.
RESULTS
Based on patient perceived outcomes (benefit:risk ratio), the most effective treatments were opioids, phenazopyridine, and alkalizing agents, with amitriptyline and antihistamines reported as moderately effective. The only surgical procedure with any effectiveness was electrocautery of Hunner's lesions. In order of efficacy reported in the literature, the therapies for IC/BPS with predicted superior outcomes should be: cyclosporine A, amitriptyline, hyperbaric oxygen, pentosan polysulfate plus subcutaneous heparin, botulinum toxin A plus hydrodistension, and L-arginine. While some of the guideline recommendations aligned with patient-reported effectiveness data, there was a general disconnect between guidelines and effectiveness reported in clinical practice.
CONCLUSIONS
There is a disconnect between real-world patient perceived effectiveness of IC/BPS treatments compared to the efficacy reported from clinical trial data and subsequent guidelines developed from this efficacy data. Optimal therapy must include the best evidence from clinical research, but should also include real-life clinical practice implementation and effectiveness.
PubMed: 29173267
DOI: 10.5489/cuaj.4505