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 IC50 values, validating this computational tool as a viable approach to predict the biological activity for inhibitors of the Rev1-CT/RIR PPI.

The development of the internet of things has led to an explosion in the number of networked devices capable of control and computing. However, whilst common place in remote sensing, these approaches have not impacted chemistry due to difficulty in developing systems flexible enough for experimental data collection. Herein we present a simple and affordable (<$500) chemistry capable robot built with a standard set of hardware and software protocols that can be networked to coordinate many chemical experiments in real time. We demonstrate how multiple processes can be done with two internet-connected robots collaboratively, exploring a set of azo-coupling reactions in a fraction of time needed for a single robot, as well as encoding and decoding information into a network of oscillating reactions. The system can also be used to assess the reproducibility of chemical reactions and discover new reaction outcomes using game playing to explore a chemical space.

Natural products are important leads in drug discovery. The search for effective plant-derived agents or their synthetic analogues has continued to be of interest to biologists and chemists for a long time. Herein, we have synthesized a novel compound, P1C, and P1C-Tit*CAgNPs from chitosan; P1C is a precursor and an anti-inflammatory candidate, which has been validated by molecular docking studies. The synthesized P1C-Tit*CAgNPs showed monodisperse, spherical, and cationic nature and antioxidant properties, protecting destabilization of the erythrocyte membrane by the azo compound 2,2'-azobis(2-amidinopropane)dihydrochloride (AAPH); the involvement of NPs as a protective agent for biomolecules, such as DNA and protein, followed by the treatment of NPs with AAPH was confirmed. The inhibition of cellular damage and leakage of cellular inflammatory agents was confirmed by AFM, SEM, TEM, SDS-PAGE, LDH, and PLA2 enzyme inhibition via in vitro studies. The anti-inflammatory property of P1C was further validated by in silico molecular docking studies and showed that, the P1C best pose aligned to PLA2 compared to standard drug. The significant anticancer property of P1C-Tit*CAgNPs was confirmed against MCF7, U373, and C6 cancer cell lines. Thus, the present study highlights the synthesized P1C in P1C-Tit*CAgNPs as a target PLA2-specific anti-inflammatory candidate, and further tuning of small and development-functionalized nanoparticles has a great future in medicine; hence, their clinical applications are warranted.

This study aimed to assess the measurement uncertainty of a new method for determination of allura redin food by high performance liquid chromatography (HPLC). The uncertainty of mathematical model of allura red is based on Europe for Analytical Chemistry(EURACHEM) guidelines. The sources and components of uncertainty were calculated, including recovery, working solution, sample mass, final volume, response of standard solution, response of sample solution. The expanded uncertainty was 0.0024 (k=2). Uncertainty of working solution was the most significant factor contributing to the total uncertainty, accounting for 86.2%. The uncertainty of volume accounted for the minimum at 0.025%. The developed method is simple and accurate, which can be used for the determination of allura redin puffed samples.

Electrochemical decolorization is of particular importance for the efficient treatment of dye wastewater. A promising electrochemical system powered by microbial fuel cells (MFCs) and intensified by Fe-C micro-electrolysis is proposed and enhanced decolorization of methyl orange (MO) is realized in this study. The decolorization efficiency reached as high as 97.1 ± 1.8% after 180 min of operation with initial MO concentration of 50 mg/L and applied voltage of 700 mV. Decolorization efficiency initially increased and then decreased with rising Fe-to-C ratio. In addition, efficiency was enhanced with the increase of aeration rate up to 6.0 L/min. Lower initial MO concentration and pH were also shown to facilitate MO decolorization. A study of mechanisms, with results from control tests and scavenger experiments indicated that MO decolorization was contributed by the indirect oxidation by various oxidizing substances, especially O2-, that were generated during the process. MO molecule was decomposed and low molecular weight compounds such as indolizine, hydrazide and thione were generated. This study advances the performance of MFC in dye wastewater treatment by combining with a standard technique.

The safety of phenazopyridine is not established in infants or during breastfeeding. Because it can cause methemoglobinemia, sulfhemoglobinemia, and hemolytic anemia, it should be avoided while breastfeeding, especially with an infant under 1 month of age or with glucose-6-phosphate dehydrogenase (G6PD) deficiency.

A series of diazenyl chalcones was prepared by base catalyzed Claisen-Schmidt condensation of synthesized hydroxy substituted acetophenone azo dye with various substituted aromatic/ heteroaromatic aldehydes. The structural conformation of synthesized chalcones was done by a number of physicochemical and spectral means like FTIR, UV-visible, mass, NMR spectroscopy and CHNS/O analysis. These diazenyl chalcones were assessed for their in vitro antimicrobial potential against several Gram-negative, Gram-positive bacterial and fungal strains by serial tube dilution method. The fluconazole and cefadroxil were used as standard drugs. The target compounds were also evaluated for their antioxidant potential by DPPH assay. (2E)-3-(2,4-Dichlorophenyl)-1-(4-((2,6- dihydroxyphenyl)diazenyl)phenyl)prop-2-en-1-one (C-7) had shown very good antimicrobial potential with MIC ranges from 3.79 to 15.76 μg/ml against most of the tested microorganisms. Most of the synthesized diazenyl chalcones were found to be active against B. subtilis. The (2E)-1-(5-((2-Chloro- 4-nitrophenyl)diazenyl)-2-hydroxyphenyl)-3-(2-hydroxynaphthalen-1-yl)prop-2-en-1-one (C-10) had shown high free radical-scavenging activity when compared with the ascorbic acid as the reference antioxidant.

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.

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-1 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-1 and 30-1000 μg L-1 ( r2 > 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.

A series of Amantadine-based azo Schiff base dyes 6a-6e have been synthesized and characterized by 1 H NMR and 13 C NMR and evaluated for their in vitro carbonic anhydrase II inhibition activity and antioxidant activity. All of the synthesized showed excellent carbonic inhibition. Compound 6b was found to be the most potent derivative in the series, and the IC50 of 6b was found to be 0.0849 ± 0.00245 μm (standard Acetazolamide IC50  = 0.9975 ± 0.049 μm). The binding interactions of the most active analogs were confirmed through molecular docking studies. Docking studies showed 6b is interacting by making two hydrogen bonds w at His93 and Ser1 residues, respectively. All compounds showed a good drug score and followed Lipinski's rule. In summary, our studies have shown that these amantadine-derived phenolic azo Schiff base derivatives are a new class of carbonic anhydrase II inhibitors.