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In medicine, barbiturates are a class of depressive medications used as hypnotics, anticonvulsants, and anxiolytics. For the treatment of specific forms of epilepsy and seizures in young children in underdeveloped countries, the World Health Organization recommends phenobarbital (PBAR), a barbiturate drug. This review describes the fabrication and characterization of a paper-based analytical apparatus for phenobarbital detection that is straightforward, affordable, portable, and disposable. All of the solid-state ion-selective electrodes (ISEs) for PBAR as well as a Ag/AgCl reference electrode were constructed and optimized on a nonconductive paper substrate. Using carbon nanotube ink, the sensors were made to function as an ion-to-electron transducer and to make the paper conductive. A suitable polymeric membrane is drop-cast onto the surface of the carbon ink orifice. The pyrido-tetrapeptide and pyrido-hexapeptide derivatives, which were recently synthesized, functioned as distinct ionophores in the PBAR-membrane sensor, enabling its detection. With a detection limit of 5.0 × 10 -7 M, the manufactured analytical device demonstrated a Nernstian response to PBAR anions in 50 mM phosphate buffer, pH 8.5, over a linear range of 1.0 × 10 -6 to 1.0 × 10 -3 M. The PBAR-based sensors showed quick (less than 5 s) response times for PBAR ion detection. The modified separate solution method was utilized to evaluate the selectivity pattern of these novel ionophores with respect to PBAR ions in comparison to other common anions. The analytical instrument that was exhibited on paper had good precision both within and between days. The suggested technology assisted in the detection of trace amounts of PBAR in real pharmaceutical samples. A comparison was made between the data acquired using the HPLC reference method and the information obtained by the recommended potentiometric approach. The described paper-based analytical device may be a good choice for point-of-care PBAR determination because it is cheap and easy to find and can self-pump (especially when combined with potentiometric detection)., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

The strategic planning of this study is based upon using the nanoformulation method to prepare nanoparticles 4-SLNs and 4-LPHNPs of the previously prepared 4,5-diphenyl-1 H -pyrazolo[3,4- c ]pyridazin-3-amine ( 4 ) after confirming its structure with single crystal X-ray analysis. These nanoparticles exhibited promising cytotoxic activity against HepG-2, HCT-116 and MCF-7 cancer cell lines in comparison with the reference doxorubicin and the original derivative 4 . Moreover, their inhibitory assessment against EGFR and CDK-2/cyclin A2 displayed improved and more favorable impact than the parent 4 and the references. Detection of their influence upon cancer biomarkers revealed upregulation of Bax, p53 and caspase-3 levels and downregulation of Bcl-2 levels. The docking simulation demonstrated that the presence of the pyrazolo[3,4- c ]pyridazin-3-amine scaffold is amenable to enclosure and binding well within EGFR and CDK-2 receptors through different hydrophilic interactions. The pharmacokinetic and physicochemical properties of target 4 were also assessed with ADME investigation, and the outcome indicated good drug-like characteristics.

One of the cardiac biomarkers, myoglobin (Mb), is important in the rapid identification of cardio-vascular disorders. Therefore, point-of-care monitoring is essential. Pursuing this goal, a robust, reliable, and affordable paper-based analytical apparatus for potentiometric sensing has been developed and characterized. The molecular imprint technique was used to create a customized biomimetic antibody for myoglobin (Mb) on the surface of carboxylated multiwalled carbon nanotubes (MWCNT-COOH). This was accomplished by attaching Mb to carboxylated MWCNTs' surfaces and then filling the empty spaces through the mild polymerization of acrylamide in N , N -methylenebisacrylamide and ammonium persulphate. The modification of the MWCNTs' surface was verified by SEM and FTIR analysis. A hydrophobic paper substrate coated with fluorinated alkyl silane (CF 3 (CF 2 ) 7 CH 2 CH 2 SiCl 3 , CF 10 ) has been coupled with a printed all-solid-state Ag/AgCl reference electrode. The presented sensors showed a linear range of 5.0 × 10 -8 to 1.0 × 10 -4 M with a potentiometric slope of -57.1 ± 0.3 mV decade -1 ( R 2 = 0.9998) and a detection limit of 28 nM at pH 4. Compared to creatinine, sucrose, fructose, galactose, sodium glutamate, thiamine, alanine, ammonium, uric acid, albumin, glutamine, guanine, troponine T, and glucose, the sensor showed good selectivity for Mb. It demonstrated a good recovery for the detection of Mb in several fake serum samples (93.0-103.3%), with an average relative standard deviation of 4.5%. The current approach might be viewed as a potentially fruitful analytical tool for obtaining disposable, cost-effective paper-based potentiometric sensing devices. These types of analytical devices can be potentially manufacturable at large scales in clinical analysis., Competing Interests: The authors declare that there are no conflicts of interest., (This journal is © The Royal Society of Chemistry.)

Some new pyridinethione and thienopyridine derivatives have been synthesized and evaluated for their antiproliferative activity using the MTT assay. Nicotinamide derivatives 3 have been synthesized and used for the preparation of new condensed thieno [2,3- b ]pyridines by their reactions with active halo compounds. Finally the synthesized thienopyridine underwent ring closure whenever possible through boiling in a solution of sodium ethoxide. The antiproliferative evaluation against (HCT-116, HepG-2, and MCF-7) human cancer cells and one human healthy cell line (BJ-1) revealed that compounds 3b , 4c - 5d , 7b - 12a , 10d , and 13b have interesting antitumor activity specifically as antihepatocellular and anticolon cellular carcinoma agents. Besides, the docking results for most active derivatives were in agreement with the in vitro antitumor results., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

A new series of benzimidazole, 1,2,4-triazole, and 1,3,5-triazine derivatives were designed and synthesized using a microwave irradiation synthetic approach utilizing 2-phenylacetyl isothiocyanate (1) as a key starting material. All the new analogues were evaluated as anticancer agents against a panel of cancer cell lines utilizing doxorubicin as a standard drug. Most of the tested derivatives exhibited selective cytotoxic activity against MCF-7 and A-549 cancer cell lines. Furthermore, the new target compounds 5 , 6 , and 7 as the most potent antiproliferative agents have been assessed as in vitro EGFR WT and EGFR T790M inhibitors compared to the reference drugs erlotinib and AZD9291. They represented more potent suppression activity against the mutated EGFR T790M than the wild-type EGFR WT . Moreover, the compounds 5 , 6 , and 7 down-regulated the oncogenic parameter p53 ubiquitination. A docking simulation of compound 6b was carried out to correlate its molecular structure with its significant EGFR inhibition potency and its possible binding interactions within the active site of EGFR WT and the mutant EGFR T790M ., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

All-solid state screen-printed electrodes were fabricated for chlorogenic acid (CGA) detection. The screen-printed platforms were modified with multi-walled carbon nanotubes (MWCNTs) to work as a lipophilic solid-contact transducer. The sensing-membrane was plasticized with a suitable solvent mediator and incorporating [Ni II (bathophenanthroline) 3 ][CGA] 2 complex as a sensory material. In a 30 mM phosphate solution (buffer, pH 6), the sensor revealed a Nernstian-response towards CGA ions with a slope of -55.1 ± 1.1 ( r 2 = 0.9997) over the linear range 1.0 × 10 -7 to 1.0 × 10 -3 (0.035-354.31 μg mL -1 ) with a detection limit 7.0 × 10 -8 M (24.8 ng mL -1 ). It revealed a stable potentiometric response with excellent reproducibility and enhanced selectivity over several common ions. Short-term potential stability and the interfacial sensor capacitance was estimated using both electrochemical-impedance spectroscopy (EIS) and chronopotentiometry techniques. The presented electrochemical platform revealed the merits of design simplicity, ease of miniaturization, good potential-stability, and cost-effectiveness. It is successfully applied to CGA determination in different coffee beans extracts and juice samples. The data obtained were compared with those obtained by liquid chromatography reference method (HPLC)., Competing Interests: The authors declare that there are no conflicts of interest. All authors have approved the manuscript and agree with the submission to your esteemed journal., (This journal is © The Royal Society of Chemistry.)

Novel paper-based potentiometric platforms for rapid, cost-effective, and simple determination of the salicylhydroxamic acid (SHAM) drug are presented. Both the SHAM sensor and the reference Ag/AgCl electrode were integrated together on the miniaturized paper platforms. The ion-sensing membrane for the presented sensor is based on the use of Sn IV -tetraphenylporphyrin (Sn IV TPP) as a charged carrier within a plasticized poly(vinyl chloride) (PVC) matrix. Multiwalled carbon nanotubes (MWCNTs) were used as an ion-to-electron transducer. The resulting sensor revealed a rapid and stable response with a Nernstian slope of -59.3 ± 0.7 mV/decade over the linear range of 1.0 × 10 -6 to 1.0 × 10 -3 M and a detection limit of 0.7 μM. All measurements were carried out in 30 mM phosphate-buffered solution (PBS) at pH 7.2. Intra- and interday precision were measured and found to be 1.7%. The relative standard deviation (RSD%) ( = 5) was calculated as 2.43% after utilizing five different electrodes ( n = 5). The selectivity behavior of the prepared electrodes in the absence and presence of ionic additives was evaluated. The selectivity pattern showed a non-Hofmeister selectivity pattern in the existence of anionic additives with enhanced potentiometric selectivity for SHAM over different lipophilic anions (e.g., ClO 4 - , SCN - , and I - ). The presented device was successfully applied for SHAM determination in pharmaceutical preparations. This paper-based analytical device can be potentially manufactured at large scales and provides a portable, rapid, disposable, and cost-effective analytical tool for measuring the SHAM drug., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

A simple, cost-effective, portable and disposable paper-based analytical device is designed and fabricated for copper(ii) determination. All solid-state ion-selective electrodes (ISEs) for copper and a Ag/AgCl reference electrode were constructed and optimized on the paper substrate. The copper electrodes were built using carbon nano-tube ink as a conductive substrate and an ion-to electron transducer. A suitable polymeric membrane is drop-cast on the surface of the conductive carbon ink window. The copper-sensing membrane is based on newly synthesized macrocyclic pyrido-pentapeptide derivatives as novel ionophores for copper detection. Under the optimized conditions, the presented all-solid-state paper-based Cu 2+ -ISEs showed a Nernstian response toward Cu 2+ ions in 30 mM MES buffer, pH 7.0 over the linear range of 5.0 × 10 -7 -1.0 × 10 -3 M with a limit of detection of 8.0 × 10 -8 M. The copper-based sensors exhibited rapid detection of Cu 2+ ions with a short response time (<10 s). The selectivity pattern of these new ionophores towards Cu 2+ ions over many common mono-, di- and trivalent cations was evaluated using the modified separate solution method (MSSM). The presented paper-based analytical device exhibited good intra-day and inter day precision. The presented tool was successfully applied for trace Cu 2+ detection in real samples of serum and whole blood collected from different children with autism spectrum disorder. The data obtained by the proposed potentiometric method were compared with those obtained by the inductively-coupled plasma (ICP) as a reference method. The presented copper paper-based analytical-device can be considered as an attractive tool for point-of-care copper determination because of its affordability, vast availability, and self-pumping ability, particularly when combined with potentiometric detection., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Herein, we describe for the first time, the design and fabrication of a novel nicotine paper-based sensor, in which a miniaturized paper reference electrode is integrated for potentiometric measurements. The paper-based sensors were designed using printed wax barriers to define the electrochemical cell and the sample zones. The electrodes were based on the use of the ion association complexes of the nicotinium cation (Nic) with either tetraphenylborate (TPB) or 5-nitrobarbiturate (NB) counter anions as sensing materials for nicotine recognition. A poly (3,4 ethylenedioxythiophene)/poly-(styrene sulfonate) (PEDOT/PSS) conducting polymer was used as an ion-to-electron transducer. The performance characteristics of the proposed sensors were evaluated and it revealed a rapid and stable response with a Nernstian slope of 55.2 ± 0.3 and 51.2 ± 0.6 mV/decade over the linear range of 1.0 × 10 -5 to 1.0 × 10 -2 M and detection limits of 6.0 and 8.0 μM for [Nic/TPB] and [Nic/NB], respectively. The sensors revealed a constant response over the pH range 3.5-6.5. The designed sensors provided a portable, inexpensive, and disposable way of measuring trace levels of nicotine coming from different cigarettes and in the collected human sweat of heavy smokers. All results were compared favorably with those obtained by the standard gas chromatographic method., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

A simple and cost-effective approach is proposed for silicate ion determination. The approach is based on designing an all-solid-state potentiometric sensor. The plasticized polyvinyl chloride (PVC) membrane sensor is based on the ion-association complex [Ni(bphen) 3 ] 2+ [SiO 3 ] 2- as a sensory recognition material. The sensor is modified with multi-walled carbon nanotubes (MWCNTs) as an ion-to-electron transducer material. The performance characteristics of the new silicate-selective electrode were evaluated using a potentiometric water-layer test, potentiometric measurements, impedance spectroscopy, and current-reversal chronopotentiometry. The developed electrodes exhibited a low detection limit (0.11 μg mL -1 ) over a wide linear range (4.0 × 10 -6 to 1.0 × 10 -3 M) and near-Nernstian sensitivity (slope = -28.1 ± 1.4 mV per decade). They presented a very short response time (<5 s) over the pH range 6-12 and provided acceptable reliability, ease of design and miniaturization, and high potential stability, in addition to good accuracy and precision. The sensors exhibited enhanced selectivity for silicate over many common interfering anions, such as SO 4 2- , NO 3 - , CH 3 COO - , CO 3 2- , Cl - , S 2- , and PO 4 3- . These results could qualify the developed sensor to be used in a successful way for the trace determination of silicate ions in different matrices. The developed method was successfully applied to the potentiometric detection of silicate in different pre-packaged bottled drinking water samples.

Herein, we used nicotinonitrile derivatives 4a , b as scaffolds to build novel and active antineoplastic agents. The reaction of nicotinonitrile derivatives 4a , b with POCl 3 /PCl 5 and/or hydrazine hydrate afforded 2-chloropyridones 6a , b and 2-hydrazinyl nicotinonitrile derivatives 11a , b , respectively, as building blocks for various heterocyclic compounds. The structures of all of the synthesized heterocycles were elucidated from their spectral and elemental analyses. The cytotoxic activities of the prepared derivatives were evaluated against different cancer cell lines. Results revealed potential cytotoxic effects of the synthesized compounds against evaluated cell lines, where NCIH 460 and RKOP 27 cell lines were the most affected by the prepared compounds. Derivative 14a was the most effective against all tested cell lines in terms of the obtained IC 50 values (25 ± 2.6, 16 ± 2, 127 ± 25, 422 ± 26, and 255 ± 2 nM against NCIH 460, RKOP 27, HeLa, U937, and SKMEL 28 cells, respectively)., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

1,4,7,10-Tetraoxa[10](2,8)trögerophane 5 was synthesized from its corresponding precursors. Heating of 2 with p-nitrophenoxide afforded bis(p-nitrophenyl)ether 3 , which was treated with hydrazine hydrate to give bis(p-aminophenyl)ether 4 . Treatment of 4 with paraformaldehyde and triflouroacetic anhydride gave trögerophane 5 . Reaction of 5 with trifluroacetic anhydride afforded phenhomazine derivative 6 , which was treated with potassium carbonate to afford tetrahydrophenhomazine 7 . Finally, reaction of 7 with phenacylchloride, bromoacetic acid, or ethyl bromoacetate in the presence of triethyl amine under reflux, afforded the corresponding macrocyclic compounds 8, 9 and 10 , respectively. The synthesized trögerophane,precursors and its newly synthesized phenhomazines derivatives were screened for anticancer activity. Results revealed that 1,4,7,10-tetraoxa[10](2,8)trögerophane had a promising selectivity towards colon cancer cell line with an IC 50 of 92.7 µg/ml., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ibrahim, Ali, Hafez, Elsayed, Mohamed, Hosni, Amr and Elsayed.)

An integrated all-solid-state screen-printed ion-selective potentiometric sensor for rapid assessment of sulfite ion in beverages, based on analytical transduction, is described. The constructed potentiometric cell incorporates a polymeric membrane sulfite ion-selective electrode based on cobalt(ii) phthalocyanine (CoPC) as a recognition material and an Ag/AgCl reference electrode with a polyvinyl butyral reference membrane. Two different solid-contact transducers, namely multi-walled carbon nanotubes (MWCNTs) and polyaniline (PANI) were used for a comparative study. The presented sensors exhibited a rapid Nernst response across the concentration ranges from 2.0 × 10 -6 to 2.3 × 10 -3 M and from 5.0 × 10 -6 to 2.3 × 10 -3 M with detection limits equal to 1.1 × 10 -6 M and 1.5 × 10 -6 M for sensors based on MWCNTs and PANI, respectively. The proposed sensors manifested high selectivity and sensitivity, enhanced stability and low cost that provides a wide number of potential applications for food analysis. Good performance characteristics were obtained for the proposed method after applying the validation requirements. Method precision, accuracy, bias, trueness, repeatability, reproducibility, and uncertainty are examined. These analytical capabilities support the rapid and direct determination of sulfite in different beverage samples. The analytical results were verified and compared with the standard iodometric method., Competing Interests: The authors declare that there are no conflicts of interest. All authors have approved the manuscript and agree with the submission to your esteemed journal., (This journal is © The Royal Society of Chemistry.)

All-solid-state potentiometric sensors have attracted great attention over other types of potentiometric sensors due to their outstanding properties such as enhanced portability, simplicity of handling, affordability and flexibility. Herein, a novel solid-contact ion-selective electrode (SC-ISE) based on poly(3,4-ethylenedioxythiophene) (PEDOT) as the ion-to-electron transducer was designed and characterized for rapid detection of harmine. The harmine-sensing membrane was based on the use of synthesized imprinted bio-mimics as a selective material for this recognition. The imprinted receptors were synthesized using acrylamide (AA) and ethylene glycol dimethacrylate (EGDMA) as functional monomer and cross-linker, respectively. The polymerization process was carried out at 70 °C in the presence of dibenzoyl peroxide (DBO) as an initiator. The sensing membrane in addition to the solid-contact layer was applied to a glassy-carbon disc as an electronic conductor. All performance characteristics of the presented electrode in terms of linearity, detection limit, pH range, response time and selectivity were evaluated. The sensor revealed a wide linearity over the range 2.0 × 10 -7 -1.0 × 10 -2 M, with a detection limit of 0.02 µg/mL and a sensitivity slope of 59.2 ± 0.8 mV/hamine concentration decade. A 40 mM Britton-Robinson (BR) buffer solution at pH of 6 was used for all harmine measurements. The electrode showed good selectivity towards harmine over other common interfering ions, and maintained a stable electrochemical response over two weeks. After applying the validation requirements, the proposed method revealed good performance characteristics. Method precision, accuracy, bias, trueness, repeatability, reproducibility, and uncertainty were also evaluated. These analytical capabilities support the fast and direct assessment of harmine in different urine specimens. The analytical results were compared with the standard liquid chromatographic method. The results obtained demonstrated that PEDOT/PSS was a promising solid-contact ion-to-electron transducer material in the development of harmine-ISE. The electrodes manifested enhanced stability and low cost, which provides a wide number of potential applications for pharmaceutical and forensic analysis.

In the present work, a new series of dihydronaphthalene derivatives were synthesized starting with 6-methoxy-1-tetralone 1 , and the corresponding hydrazine derivative 2 . Reaction of compound 2 with aryl isothiocyanates produced thiosemicarbazides 3a-d , which were reacted with ethyl chloroacetate to give thiazolidinone derivatives 4a-d . Pyrano thiazolecarbonitrile derivatives 5a - f were prepared by heating a mixture of compounds 4a or 4c , aryl aldehydes, and malononitrile utilizing distilled water in the presence of catalytic amount of potassium hydrogen phthalate. Also, treatment of 4a with DMF-DMA under solvent-free conditions gave enaminone derivative 6 , which condensed with ethyl acetoacetate or acetylacetone or malononitrile or cyanothioacetamide to give compounds 7 - 10 , respectively. Finally, reaction of the enaminone 6 with 2-aminoimidazol or 2-aminothiazol in the presence of glacial acetic acid produced derivatives 11 and 12 , respectively. Cytotoxic evaluation of eleven compounds, against MCF-7 (human breast adenocarcinoma) cell lines, was estimated. Results revealed that five of the examined compounds 5a , 5d , 5e , 10 , and 3d showed potent cytotoxic activities recording, IC 50 values; 0.93 ± 0.02, 1.76 ± 0.04, 2.36 ± 0.06, 2.83 ± 0.07, and 3.73 ± 0.09  μ M, respectively, which were more potent than the reference used (Saturosporin, IC 50 6.08 ± 0.15  μ M). The new products were also examined towards normal epithelial breast cells (MCF10A). All of them showed very good safety profile with different degrees and were safer than the reference drug used. Compound 5a was the most effective against MCF-7 cells and was less toxic than Saturosporin by about 18.45-folds towards MCF01A normal cells. All the new compounds were fully characterized by the different spectral and analytical tools. Herein, detailed syntheses, spectroscopic, and biological data are reported., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Nesreen S. Ahmed et al.)

A novel series of pyrazole analogues including hydrazones, pyrazolo[4,3- c ]-pyridazines, pyrazolo[3,4- e ][1,2,4]triazine and pyrazolo[3,4- d ][1,2,3]triazoles was designed, synthesised and screened for their in vitro antimicrobial and DHFR inhibition activity. Compounds bearing benzenesulphonamide moiety incorporated with 3-methyl-5-oxo-1 H -pyrazol-4(5 H )-ylidene) hydrazine 3a or 6-amino-7-cyano-3-methyl-5 H -pyrazolo[4,3- c ]pyridazine 6a revealed excellent and broad spectrum antimicrobial activity comparable to ciprofloxacin and amphotericin B as positive antibiotic and antifungal controls, respectively. Furthermore, these derivatives proved to be the most active DHFR inhibitors with IC 50 values 0.11 ± 1.05 and 0.09 ± 0.91 µM, in comparison with methotrexate (IC 50 = 0.14 ± 1.25 µM). The in silico studies were done to calculate the drug-likeness and toxicity risk parameters of the newly synthesised derivatives. Additionally, the high potency of the pyrazole derivatives bearing sulphonamide against DHFR was confirmed with molecular docking and might be used as an optimum lead for further modification.

Solid-contact ion-selective electrodes (SC-ISEs) have shown great potential for routine and portable ion detection. The introduction of nanomaterials as ion-to-electron transducers and the adoption of different performance-enhancement strategies have significantly promoted the development of SC-ISEs. Herein, new solid-contact ion-selective electrodes, along with the implementation of multiwalled carbon nanotubes (MWCNTs) as ion-to-electron transducers and potassium tetrakis (p-chlorophenyl) borate (KTpClB) as lipophilic ionic additives, were presented for the detection of isoproturon (IPU) and diuron (DU) herbicides. Molecularly imprinted polymers (MIPs), with special molecule recognition properties for isoproturon (IPU) and diuron (DU), were prepared, characterized, and introduced as sensory recognition materials in the presented electrodes. Sensors revealed a near-Nernstian response for both isoproturon (IPU) and diuron (DU) with slopes of 53.1 ± 1.2 ( r 2 = 0.997) and 57.2 ± 0.3 ( r 2 = 0.998) over the linear ranges of 2.2 × 10 -6 -1.0 × 10 -3 M and 3.2 × 10 -6 -1.0 × 10 -3 M with detection limits of 8.3 × 10 -7 and 1.4 × 10 -6 M, respectively. The response time of the presented sensors was found to be <5 s and the lifetime was at least eight weeks. The sensors exhibited good selectivity towards isoproturon (IPU) and diuron (DU) in comparison with some other herbicides, alkali, alkaline earth, and heavy metal ions. The presented sensors were successfully applied for the direct determination of isoproturon (IPU) and diuron (DU) in real water samples.

A simple, rapid, sensitive, and precise reversed-phase liquid chromatographic method was developed and validated for the simultaneous determination of four direct-acting antivirals, sofosbuvir (SF), ledipasvir (LD), declatasvir (DC), and simeprevir (SM), in their respective pharmaceutical formulations. Effective chromatographic separation was achieved on an Agilent Eclipse plus C8 column (250 mm × 4.6 mm, 5 µm) at 40 °C with gradient elution using a mobile phase composed of acetonitrile:phosphate buffer (pH 6.5). The quantification of SF and DC was based on peak area measurements at 260 nm, while the quantification of LD and SM was achieved at 330 nm. The linearity was acceptable from 1.0 to 20.0 μg/mL for the studied drugs, with correlation coefficients >0.999. The analytical performance of the newly proposed HPLC procedure was thoroughly validated according to ICH guidelines in terms of linearity, precision (RSD%, 0.39-1.57), accuracy (98.05-101.90%), specificity, limit of detection (LOD) (0.022-0.039 μg/mL), limit of quantification (LOQ) (0.067-0.118 μg/mL), and robustness. The validated HPLC method was successfully used to analyze the abovementioned drugs in their pure and dosage forms without interference from common excipients present in commercial formulations.

Herein, a novel validated potentiometric method is presented for the first time for citicoline determination. The method is based on measuring the potential using new constructed citicoline electrodes. The electrodes are based on the use of citicolinium/phosphomolybdate [Cit] 2 [PM] (sensor I) and citicolinium/tetraphenylborate [Cit][TPB] (sensor II) ion association complexes. These sensory materials were dispersed in plasticized polyvinyl chloride (PVC) polymeric membranes. The sensors revealed a Nernstian response with the slopes 55.9 ± 1.8( r 2 = 0.9994) and 51.8 ± 0.9 ( r 2 = 0.9991) mV/decade over a linearity range of 6.3 × 10 -6 -1.0 × 10 -3 and 1.0 × 10 -5 -1.0 × 10 -3 M and detection limits of 3.16 × 10 -6 and 7.1 × 10 -6 M for sensors I and II, respectively. To ensure the existence of monovalent citicoline, all measurements were performed in 50 mM acetate buffer at pH 3.5. All presented electrodes showed good performance characteristics such as rapid response, good selectivity, high potential-stability and long life-span. Method verification and validation in terms of response linearity, quantification limit, accuracy, bias, trueness, robustness, within-day variability and between-days variability were evaluated. The method was introduced for citicoline determination in different pharmaceutical formulations and compared with the standard high performance liquid chromatography (HPLC) method.

Novel potentiometric devices "ion-selective electrodes (ISEs)" were designed and characterized for the detection of 17β-estradiol (EST) hormone. The selective membranes were based on the use of man-tailored biomimics (i.e., molecularly imprinted polymers (MIPs)) as recognition ionophores. The synthesized MIPs include a functional monomer (methacrylic acid (MAA)) and a cross-linker (ethylene glycol dimethacrylic acid (EGDMA)) in their preparation. Changes in the membrane potential induced by the dissociated 17β-estradiol were investigated in 50 mM CO 3 2- /HCO 3 - buffer solution at pH 10.5. The ion-selective electrodes (ISEs) exhibited fast response and good sensitivity towards 17β-estradiol with a limit of detection 1.5 µM over a linear range starts from 2.5 µM with an anionic response of 61.2 ± 1.2 mV/decade. The selectivity pattern of the proposed ISEs was also evaluated and revealed an enhanced selectivity towards EST over several phenolic compounds. Advantages revealed by the presented sensor (i.e., wide range of assay, enhanced accuracy and precision, low limit of detection, good selectivity, long-term potential stability, rapid response and long life-span and absence of any sample pretreatment steps) suggest its use in routine quality control/quality assurance tests. They were successfully applied to estradiol determination in biological fluids and in different pharmaceutical preparations collected from the local market.

A simple potentiometric sensor is described for accurate, precise, and rapid determination of sulfite additives in beverages. The sensor is based on the use of cobalt phthalocyanine as a recognition material, dispersed in a plasticized poly(vinyl chloride) matrix membrane. o -Nitrophenyl octyl ether ( o -NPOE) as a membrane solvent and tri-dodecylmethyl- ammonium chloride (TDMAC) as ion discriminators are used as membrane additives. Under the optimized conditions, sulfite ion is accurately and precisely measured under batch and flow injection modes of analysis. The sensor exhibits fast and linear response for 1.0 × 10 -2 -1.0 × 10 -6 M (800-0.08 µg/mL) and 1.0 × 10 -1 -5.0 × 10 -5 M (8000-4 µg/mL) sulfite with Nernstian slopes of -27.4 ± 0.3 and -23.7 ± 0.6 mV/concentration decade under static and hydrodynamic modes of operation, respectively. Results in good agreement with the standard iodometric method are obtained.Validation of the assay method is examined in details including precision, accuracy, bias, trueness, repeatability, reproducibility, and uncertainty and good performance characteristics of the method are obtained. The sensor response is stable over the pH range of 5 to 7 without any significant interference from most common anions. The advantages offered by the proposed sensor (i.e., wide range of assay, high accuracy and precision, low detection limit, reasonable selectivity, long term response stability, fast response, and long life span and absence of any sample pretreatment steps) suggest its use in the quality control/quality assurance routine tests in beverages industries, toxicological laboratories and by inspection authorities.

Herein, we present for the first time a novel potentiometric sensor based on the stimulus-responsive molecularly imprinted polymer (MIP) as a selective receptor for neutral dopamine determination. This smart receptor can change its capabilities to recognize according to external environmental stimuli. Therefore, MIP-binding sites can be regenerated in the polymeric membrane by stimulating with stimulus after each measurement. Based on this effect, reversible detection of the analyte via potentiometric transduction can be achieved. MIPs based on 4-vinylphenylboronic acid as the functional monomer were prepared as the selective receptor. This monomer can successfully bind to dopamine via covalent binding and forming a five- or six-membered cyclic ester in a weakly alkaline aqueous solution. In acidic medium, the produced ester dissociates and regenerates new binding sites in the polymeric membrane. The proposed smart sensor exhibited fast response and good sensitivity towards dopamine with a limit of detection 0.15 µM over the linear range 0.2-10 µM. The selectivity pattern of the proposed ISEs was also evaluated and revealed an enhanced selectivity towards dopamine over several phenolic compounds. Constant-current chronopotentiometry is used for evaluating the short-term potential stability of the proposed ISEs. The obtained results confirm that the stimulus-responsive MIPs provide an attractive way towards reversible MIP-based electrochemical sensors designation., Competing Interests: The authors declare no conflicts of interest.

To develop new antimicrobial agents, a series of novel thiourea derivatives incorporated with different moieties 2-13 was designed and synthesized and their biological activities were evaluated. Compounds 7a , 7b and 8 exhibited excellent antimicrobial activity against all Gram-positive and Gram-negative bacteria, and the fungal Aspergillus flavus with minimum inhibitory concentration (MIC) values ranged from 0.95 ± 0.22 to 3.25 ± 1.00 μg/mL. Furthermore, cytotoxicity studies against MCF-7 cells revealed that compounds 7a and 7b were the most potent with IC 50 values of 10.17 ± 0.65 and 11.59 ± 0.59 μM, respectively. On the other hand, the tested compounds were less toxic against normal kidney epithelial cell lines (Vero cells). The in vitro enzyme inhibition assay of 8 displayed excellent inhibitory activity against Escherichia coli DNA B gyrase and moderate one against E. coli Topoisomerase IV (IC 50 = 0.33 ± 1.25 and 19.72 ± 1.00 µM, respectively) in comparison with novobiocin (IC 50 values 0.28 ± 1.45 and 10.65 ± 1.02 µM, respectively). Finally, the molecular docking was done to position compound 8 into the E. coli DNA B and Topoisomerase IV active pockets to explore the probable binding conformation. In summary, compound 8 may serve as a potential dual E. coli DNA B and Topoisomerase IV inhibitor.

A simple, rapid and easy method is proposed for the detection of a cytostatic therapeutic drug, cytarabine, in real samples. The method is based on potentiometric transduction using prepared and characterized new ion-selective electrodes for cytarabine. The electrodes were integrated with novel man-tailored imprinted polymers and used as a sensory element for recognition. The electrodes revealed a remarkable potentiometric response for cytarabine over the linearity range 1.0 × 10 -6 -1.0 × 10 -3 M at pH 2.8-4 with a detection limit of 5.5 × 10 -7 M. The potentiometric response was near-Nernstian, with average slopes of 52.3 ± 1.2 mV/decade. The effect of lipophilic salts and plasticizer types on the potentiometric response was also examined. The electrodes exhibited an enhanced selectivity towards cytarabine over various foreign common ions. Validation and verification of the presented assay method are demonstrated by evaluating the method ruggedness and calculating the detection limit, range of linearity, accuracy (trueness), precision, repeatability (within-day) and reproducibility (between-days). The proposed ion-selective electrodes revealed good performance characteristics and possible application of these electrodes for cytarabine monitoring in different matrices. The electrodes are successfully applied to cytarabine determination in spiked biological fluid samples and in pharmaceutical formulations.

Copper ferrite nano-particles (CuFe 2 O 4 ) were synthesized, characterized, modified with polyaniline to form CuFe 2 O 4 /PANI nano-composite. They were used as new adsorbents for the removal of the hazardous mercuric ions from aqueous solutions. High resolution transmission electron microscope (HR-TEM), X-ray diffraction (XRD), Fourier-transform infrared (FT-IR) and Brunauer-Emmett-Teller (BET) were used for the characterization of the synthesized CuFe 2 O 4 nano-particles (NPs) in presence and absence of PANI nano-composite. The synthesized CuFe 2 O 4 NPs were of spherical shape with an average size of 10.8 nm. XRD analysis displayed crystal peaks for CuFe 2 O 4 NPs and amorphous peaks CuFe 2 O 4 /PANI nano-composite due to the existence of polyaniline layer. Contact time, adsorbent dose, solution pH, adsorption kinetics, adsorption isotherm and recyclability were studied. The method at the optimum conditions exhibited high performance with high mercury removal percentage of up to 99% with a maximum adsorption capacity 12.5 and 157.1 mg/g for CuFe 2 O 4 and CuFe 2 O 4 /PANI, respectively. The adsorption processes were fitted to Langmuir isotherms. The adsorption behavior of CuFe 2 O 4 @PANI composite towards Hg 2+ ions is attributed to the soft acid-soft base strong interaction between PANI and Hg(II) ions. High stability and enhanced re-usability are offered using CuFe 2 O 4 @PANI composite due to its enhanced removal efficiency. No significant removal decrease was noticed after five adsorption-desorption cycles. In addition, it possesses an easy removal from aqueous solutions by external magnetic field after adsorption experiments. These indicated the enhancement of polyaniline to the surface of CuFe 2 O 4 toward the adsorption of mercury from aqueous solutions.

A facile eco-friendly approach for acetampirid pesticide removal is presented. The method is based on the use of micro- and mesoporous activated carbon (TPAC) as a natural adsorbent. TPAC was synthesized via chemical treatment of tangerine peels with phosphoric acid. The prepared activated carbon was characterized before and after the adsorption process using Fourier- transform infrared (FTIR), X-ray diffraction (XRD), particle size and surface area. The effects of various parameters on the adsorption of acetampirid including adsorbent dose (0.02-0.2 g), pH 2-8, initial adsorbate concentration (10-100 mg/L), contact time (10-300 min) and temperature (25-50 °C) were studied. Batch adsorption features were evaluated using Langmuir and Freundlich isotherms. The adsorption process followed the Langmuir isotherm model with a maximum adsorption capacity of 35.7 mg/g and an equilibration time within 240 min. The adsorption kinetics of acetamiprid was fitted to the pseudo-second-order kinetics model. From the thermodynamics perspective, the adsorption was found to be exothermic and spontaneous in nature. TPAC was successfully regenerated and reused for three consecutive cycles. The results of the presented study show that TPAC may be used as an effective eco-friendly, low cost and highly efficient adsorbent for the removal of acetamiprid pesticides from aqueous solutions.

In this research, CuFe 2 O 4 nanoparticles were synthesized by co-precipitation methods and modified by coating with thiophene for removal of Hg(II) ions from aqueous solution. CuFe 2 O 4 nanoparticles, with and without thiophene, were characterized by x-ray diffraction (XRD), Field emission scanning electron microscopy (FESEM), energy dispersive x-ray (EDX), high-resolution transmission electron microscopy (HRTEM) and Brunauer-Emmett-Teller (BET). Contact time, adsorbent dose, solution pH, adsorption kinetics, adsorption isotherm and recyclability were studied. The maximum adsorption capacity towards Hg 2+ ions was 7.53 and 208.77 mg/g for CuFe 2 O 4 and CuFe 2 O 4 @Polythiophene composite, respectively. Modification of CuFe 2 O 4 nanoparticles with thiophene revealed an enhanced adsorption towards Hg 2+ removal more than CuFe 2 O 4 nanoparticles. The promising adsorption performance of Hg 2+ ions by CuFe 2 O 4 @Polythiophene composite generates from soft acid-soft base strong interaction between sulfur group of thiophene and Hg(II) ions. Furthermore, CuFe 2 O 4 @Polythiophene composite has both high stability and reusability due to its removal efficiency, has no significant decrease after five adsorption-desorption cycles and can be easily removed from aqueous solution by external magnetic field after adsorption experiments took place. Therefore, CuFe 2 O 4 @Polythiophene composite is applicable for removal Hg(II) ions from aqueous solution and may be suitable for removal other heavy metals.

Herein, we present a new validated potentiometric method for fluoxetine (FLX) drug monitoring. The method is based on the integration of molecular imprinting polymer (MIP) beads as sensory elements with modified screen-printed solid contact ion-selective electrodes (ISEs). A multi-walled carbon nanotube (MWCNT) was used as a nanomaterial for the ion-to-electron transduction process. The prepared MIP beads depend on the use of acrylamide (AAm) and ethylene glycol dimethacrylic acid (EGDMA) as a functional monomer and cross-linker, respectively. The sensor revealed a stable response with a Nernstian slope of 58.9 ± 0.2 mV/decade and a detection limit of 2.1 × 10 -6 mol/L in 10 mmol/L acetate buffer of pH 4.5. The presented miniaturized sensors revealed good selectivity towards FLX over many organic and inorganic cations, as well as some additives encountered in the pharmaceutical preparations. Repeatability, reproducibility and stability have been studied to evaluate the analytical features of the presented sensors. These sensors were successfully applied for FLX assessment in different pharmaceutical formulations collected from the Egyptian local market. The obtained results agreed well with the acceptable recovery percentage and were better than those obtained by other previously reported routine methods.

A simple, efficient and reliable analytical method was developed and used for the determination of the fluvoxamine drug (FLV) in pharmaceutical preparations and biological fluids. The method is based on the cost-effective screen-printed platform for the potential transduction of the drug. Host-tailored molecular imprinting polymer (MIP) was integrated with the potentiometric platform as a recognition receptor, in which FLV, acrylamide (AAm), ethylene glycol dimethacrylate (EGDMA) and acetonitrile were used as a template, functional monomer, cross-linker, and solvent, respectively. MIP particles were dispersed in plasticized poly (vinyl chloride) (PVC) and the membrane was drop-casted on carbon screen-printed electrode. The MIP, in addition to non-imprinted polymers (NIP), was characterized and the binding experiment revealed high affinity and adsorption capacity of MIP towards FLV. The proposed sensor displayed near-Nernstian cationic slope of 55.0 ± 0.8 mV/decade ( r 2 = 0.999) with a low detection limit of 4.8 × 10 -6 mol/L over a wide pH range (3.0-8.5). The electrochemical features of the proposed sensors including electrochemical impedance spectroscopy (EIS) and chronopotentiometry measurements (CP) in the presence of multi-walled carbon nanotubes (MWCNTs) as a solid contact transducer were also investigated. The applications of the proposed sensor for the determination of FLV in different dosage forms with recovery values (98.8%-101.9%) and (97.4%-101.1%), respectively compared with the reference HPLC method with acceptedFandt-student tests values at the 95% confidence level., Competing Interests: The authors declare no conflicts of interest.

As important cancer therapeutic agents, macrocyclic peptides have recently drawn great attention, mainly because they are synthetically accessible and have lower toxicity towards normal cells. In the present work, we synthesized newly macrocyclic pyridoheptapeptide derivatives. The synthesized derivatives were characterized using standard chemical and spectroscopic analytical techniques, and their anticancer activities against human breast and hepatocellular cancer cells were investigated. Results showed that compounds 1a and 1b were the most effective against hepatocellular (HepG2) and breast (MCF-7) cancer cell lines, respectively.

A series of branched tetrapeptide Schiff bases 3 - 6 were designed and synthesized from corresponding tetrapeptide hydrazide 2 as a starting material.In vitroevaluation of the synthesized compounds 4 - 6 against breast MCF-7 carcinoma cells identified their excellent anticancer potency, with IC 50 ranging from 8.12 ± 0.14 to 17.55 ± 0.27 μM in comparison with the references, cisplatin and milaplatin (IC 50 = 13.34 ± 0.11and 18.43 ± 0.13 μM, respectively). Furthermore, all derivatives demonstrated promising activity upon evaluation of theirin vitroandin vivosuppression of p53 ubiquitination and inhibition assessment for LDHA kinase. Finally, molecular docking studies were performed to predict the possible binding features of the potent derivatives within the ATP pocket of LDHA in an attempt to get a lead for developing a more potent LDHA inhibitor with anti-proliferative potency.

Screen-printed platforms integrated with molecularly imprinted polymers (MIP) were fabricated and characterized as potentiometric sensors for diquat (DQ). The synthesized MIP beads were studied as sensory carriers in plasticized poly(vinyl chloride) membranes. The sensors were constructed by using poly(3,4-ethylenedioxythiophene) (PEDOT) as solid-contact material to diminish charge-transfer resistance and water layer potential. Conventional ion-selective electrodes (ISEs) with internal filling solution were used for comparison. The designed electrodes showed near Nernstian slopes of 28.2 ± 0.7 (r² = 0.999) over the concentration range of 1.0 × 10 -6 -1.0 × 10 -2 M with the limit of detection 0.026 µg/mL over the pH range 4.2-9.0. The electrode exhibited good selectivity for diquat cations over a large number of organic and inorganic cations. The sensor was successfully introduced for direct measurement of diquat content in commercial pesticide preparations and different spiked potato samples. The results showed that the proposed electrode has a fast and stable response, good reproducibility, and applicability for direct assessment of diquat content. The proposed potentiometric method is simple and accurate in comparison with the reported HPLC methods. Besides, it is applicable to turbid and colored sample solutions., Competing Interests: The authors declare no conflict of interest.

Potentiometric sensors have a great influence on the determination of most various compounds in their matrices. Therefore, efficient and new sensors were introduced to measure sodium Deoxycholate (NaDC) as a bile acid salt. These sensors are based on NaDC imprinted polymer (MIP) as sensory element. The MIP beads were synthesized using thermal polymerization pathway, in which acrylamide (AAm), ethylene glycol dimethacrylate (EGDMA), NaDC, and benzoyl peroxide (BPO) were used as the functional monomer, cross-linker, template, and initiator, respectively. The proposed sensors were fabricated using a coated screen-printed platform and the sensing membrane was modified by single-walled carbon nanotubes (SWCNTs) as an ion-to-electron transducer. The sensors exhibited high sensitivity that reached 4.7 × 10 -5 M of near-Nernestian slope (-60.1 ± 0.9 mV/decade, r 2 = 0.999 ( n = 5)). In addition, the sensors revealed high selectivity, long lifetime, high potential stability, and conductivity that ensure reproducible and accurate results over a long time. MIP characterization was performed using Fourier Transform-Infrared (FT-IR) and a scanning electron microscope (SEM). Regarding the interaction of NaDC with serum albumin (SA), albumin is determined in human serum samples as human serum albumin (HSA), which was collected from different volunteers of different ages and gender., Competing Interests: The authors declare no conflict of interest.

A new SnO 2 /CeO 2 nano-composite catalyst was synthesized, characterized and used for the removal of alizarin dyes from aqueous solutions. The composite material was prepared using a precipitation method. X-ray powder diffractometry (XRD), high resolution transmission electron microscopy (HR-TEM), Brunauer-Emmett-Teller methodology (BET) and Fourier Transform Infrared Spectrometry (ATR-FTIR) were utilized for the characterization of the prepared composite. The prepared nano-composite revealed high affinity for the adsorption and decomposition of alizarin dyes. The adsorption capacity under different experimental conditions (adsorbate concentration, contact time, adsorbent dose and pH) was examined. Under optimized experimental conditions, the removal of alizarin yellow, alizarin red and alizarin-3-methylimino-diacetic acid dyes from aqueous solutions was about 96.4%,87.8% and 97.3%, respectively. The adsorption isotherms agreed with the models of Langmuir, Freundlich and Temkin isotherms., Competing Interests: The authors declare no conflict of interest.

Screen-printed membrane sensors based on the use of paper and ceramic substrates are fabricated, characterized, and used for rapid batch and continuous monitoring of Cr III in the form of CrO 4 2- in some industrial products and wastewater samples. Strips of paper and ceramic platforms (15 × 5 mm) were covered with conductive carbon paint and then modified with polyaniline (PANI) film, to act as an ion-to-electron transducer, followed by a drop casting of plasticized poly (vinyl chloride) (PVC) Rhodamine-B chromate membrane as a recognition sensing material. In a 5.0 mmol L -1 Trizma buffer solution of pH ~8, the fabricated paper and ceramic based membrane sensors exhibited a near Nernstian response for Cr VI ion with slopes of -29.7 ± 0.5 and -28.6 ± 0.3 mV decade -1 , limit of detection 2.5 × 10 -5 and 2.4 × 10 -6 mol L -1 (1.3-0.12 µg mL -1 ), and linear concentration range 7.5 × 10 -3 -5.0 × 10 -5 and 7.5 × 10 -3 -1.0 × 10 -5 mol L -1 (390-0.5 µg mL -1 ), respectively. Both sensors exhibited fast and stable potentiometric response, excellent reproducibility, and good selectivity with respect to a number of common foreign inorganic species. Impedance spectroscopy and chronopotentiometry data revealed a small resistance and a larger double layer capacitance due to the presence of the intermediate polyaniline (PAN) conductive layer. Furthermore, the formation of a water layer between the ion selective membrane (ISM) and the underlying conductor polymer and between the conducting polymer and the carbon conducting surface was greatly reduced. The developed disposable solid-contact potentiometric sensors offer the advantages of simple design, long term potential stability, flexibility, miniaturization ability, short conditioning time, and cost effectiveness that enable mass production. The sensors were successfully used for static and hydrodynamic measurements of total chromium in some leather tanning wastewater and nickel-chrome alloy samples. The results compare favorably with data obtained by atomic absorption spectrometry., Competing Interests: The authors declare no conflict of interest.

Pyrazolylphthalimide derivative 4 was synthesized and reacted with different reagents to afford the target compounds imidazopyrazoles 5-7 , pyrazolopyrimidines 9, 12, 14 and pyrazolotriazines 16, 17 containing phthalimide moiety. The prepared compounds were established by different spectral data and elemental analyses. Additionally, all synthesized derivatives were screened for their antibacterial activity against four types of Gram + ve and Gram-ve strains, and for antifungal activity against two fungi micro-organisms by well diffusion method. Moreover, the antiproliferative activity was tested for all compounds against human liver (HepG-2) cell line in comparison with the reference vinblastine. Moreover, drug-likeness and toxicity risk parameters of the newly synthesized compounds were calculated using in silico studies. The data from structure-actvity relationship (SAR) analysis suggested that phthalimide derivative bearing 3-aminopyrazolone moiety, 4 illustrated the best antimicrobial and antitumor activities and might be considered as a lead for further optimization. To investigate the mechanism of the antimicrobial and anticancer activities, enzymatic assay and molecular docking studies were carried out on E. coli topoisomerase II DNA gyrase B and VEGFR-2 enzymes.

Novel potentiometric solid-contact ion-selective electrodes (SC/ISEs) based on molecularly imprinted polymers (MIPs) as sensory carriers (MIP/PANI/ISE) were prepared and characterized as potentiometric sensors for flucarbazone herbicide anion. However, aliquat S 336 was also studied as a charged carrier in the fabrication of Aliquat/PANI/ISEs for flucarbazone monitoring. The polyaniline (PANI) film was inserted between the ion-sensing membrane (ISM) and the electronic conductor glassy carbon substrate (GC). The sensors showed a noticeable response towards flucarbazone anions with slopes of -45.5 ± 1.3 (r 2 = 0.9998) and -56.3 ± 1.5 (r 2 = 0.9977) mV/decade over the range of 10 -2 -10 -5 , 10 -2 -10 -4 M and detection limits of 5.8 × 10 -6 and 8.5 × 10 -6 M for MIP/PANI/ISE and Aliguat/PANI/ISE, respectively. The selectivity and long-term potential stability of all presented ISEs were investigated. The short-term potential and electrode capacitances were studied and evaluated using chronopotentiometry and electrochemical impedance spectrometry (EIS). The proposed ISEs were introduced for the direct measurement of flucarbazone herbicide in different soil samples sprayed with flucarbazone herbicide. The results agree well with the results obtained using the standard liquid chromatographic method (HPLC)., Competing Interests: The authors declare no conflicts of interest.

The current study was chiefly designed to examine the antiproliferative and antioxidant activities of some novel quinazolinone(thione) derivatives 6 - 14 . The present work focused on two main points; firstly, comparing between quinazolinone and quinazolinthione derivatives. Whereas, antiproliferative (against two cell lines namely, HepG2 and MCF-7) and antioxidant (by two methods; ABTS and DPPH) activities of the investigated compounds, the best quinazolinthione derivatives were 6 and 14, which exhibited excellent potencies comparable to quinazolinone derivatives 5 and 9 , respectively. Secondly, we compared the activity of four series of Schiff bases which included the quinazolinone moiety ( 11a - d ). In addition, the antiproliferative and antioxidant activities of the compounds with various aryl aldehyde hydrazone derivatives ( 11a - d ) analogs were studied. The compounds exhibited potency that increased with increasing electron donating group in p -position (OH > OMe > Cl) due to extended conjugated systems. Noteworthy, most of antiproliferative and antioxidant activities results for the tested compounds are consistent with the DFT calculations.

Possible improvement of the performance characteristics, reliability and selectivity of solid-contact nitrate ion-selective electrodes (ISE) (SC/NO 3 - -ISE) is attained by the application of a nitron-nitrate (Nit + /NO 3 - ) ion association complex and inserting multi-walled carbon nanotubes (MWCNTs) as an ion-to-electron transducer between the ion sensing membrane (ISM) and the electronic conductor glassy carbon (GC) substrate. The potentiometric performance of the proposed electrode revealed a Nernstian slope -55.1 ± 2.1 (r² = 0.997) mV/decade in the range from 8.0 × 10 - 8 -1 × 10 - 2 M with a detection limit of 2.8 × 10 - 8 (1.7 ng/mL). Selectivity, repeatability and reproducibility of the proposed sensors were considerably improved as compared to the coated disc electrode (GC/NO 3 - -ISE) without insertion of a MWCNT layer. Short-term potential stability and capacitance of the proposed sensors were tested using a current-reversal chronopotentiometric technique. The potential drift in presence of a MWCNT layer decreased from 167 μVs - 1 (i.e., in absence of MWCNTs) to 16.6 μVs - 1 . In addition, the capacitance was enhanced from 5.99 μF (in absence of MWCNTs) to 60.3 μF (in the presence of MWCNTs). The presented electrodes were successfully applied for nitrate determination in real samples with good accuracy., Competing Interests: The authors declare no conflicts of interest.

Solid-contact potentiometric ion-selective electrodes (SC-ISEs) for thallium determination have been designed using multiwall carbon nanotubes (MWCNTs) as the ion-to-electron transducer. Dispersed MWCNTs were drop-casted over a gold plate electrode. Two different crown ethers were used in the sensing membrane for the recognition of thallium (I). Sensorsbased on dibenzo-18-crown-6 (DB18C6) as a neutral carrier and NaTPB as an anionic additive exhibited a near Nernstian response of 57.3 mV/decade towards Tl + ions over the activity range 4.5 × 10 -6 -7.0 × 10 -4 M, with a limit of detection of 3.2 × 10 -7 M. The time required to achieve 95% of the steadyequilibrium potential was <10 s. The complex formation constant (log β ML ) between dibenzo-18-crown-6 and thallium (I) (i.e., 5.99) was measured using the sandwich membrane technique. The potential response was pH independent over the range 3.0-9.5. The introduction of MWCNTs as an electron-ion-transducer layer between gold plate and the sensing membrane lead to a smaller membrane resistance and a large double layer capacitance, which was proven using impedance spectra and chronopotentiometry (i.e., 114.9 ± 12 kΩ, 52.1 ± 3.3 pF, 200 ± 13.2 kΩ, and 50 ± 4.2 µF). Additionally, reduction ofthe water layer between the sensing membrane and the underlying conductor wastested. Thus, it is clear that MWCNTs can be used as a transducing layer in SC-ISEs. The proposed sensor was introduced as an indicator electrode for potentiometric titration of single and ternary mixtures of I - , Br - , and S 2- anions.

Breast cancer is considered the most common and deadly cancer among women worldwide. Nanomedicine has become extremely attractive in the field of cancer treatment. Due to the high surface to volume ratio and other unique properties, nanomaterials can be specifically targeted to certain cells and tissues to interact with the living systems. The strategic planning of this study is based on using the nanoprecipitation method to prepare nanoparticles BZP-NPs (3.8-5.7 nm) of the previously prepared benzofuran-pyrazole compound ( IV ) BZP which showed promising cytotoxic activity. The capacity of BZP and BZP-NPs to suppress the growth of human breast tumor MCF-7 and MDA-MB-231 cells was evaluated using MTT assay. The IC 50 doses of BZP and BZP-NPs targeting normal breast cells MCF-12A exceeded those targeting the cancer cells by >1000-fold, demonstrating their reasonable safety profiles in normal cells. Furthermore, cell cycle analysis, apoptosis induction detection, assessment of p53, Bcl-2, caspase-3, and PARP-1 levels of BZP and its nano-sized- BZP-NPs particles were also evaluated. Although the obtained results were in the favor of compound IV in its normal-sized particles, BZP-NPs appeared as a hit compound which showed improved cytotoxicity against the tested human breast cancer cells associated with the induction of pre-G1 apoptosis as well as cell cycle arrest at G2/M phase. The increase in caspase-3 level, upregulation of p53, and downregulation of Bcl-2 protein expression levels confirmed apoptosis. Furthermore, ELISA results exhibited that BZP-NPs produced a more favorable impact as a PARP-1 enzyme inhibitor than the parent BZP .

In this study, some of new thiophenyl thienopyrimidinone derivatives 2 - 15 were prepared and tested as anti-cancer agents by using thiophenyl thieno[2,3-d]pyrimidinone derivative 2 as a starting material, which was prepared from cyclization of ethyl ester derivative 1 with formamide. Treatment of 2 with ethyl- chloroacetate gave thienopyrimidinone N -ethylacetate 3 , which was reacted with hydrazine hydrate or anthranilic acid to afford acetohydrazide 4 and benzo[d][1, 3 ]oxazin-4-one 5, respectively. Condensation of 4 with aromatic aldehydes or phenylisothiocyanate yielded Schiff base derivatives 6,7 , and thiosemicarbazise 10 , which were treated with 2-mercaptoacetic acid or chloroacetic acid to give the corresponding thiazolidinones 8 , 9, and phenylimino-thiazolidinone 11 , respectively. Treatment of 4 with ethylacetoacetate or acetic acid/acetic anhydride gave pyrazole 12 and acetyl acetohydrazide 13 derivatives, respectively. The latter compound 13 was reacted with ethyl cycno-acetate or malononitrile to give 14 and 15 , respectively. In this work, we have studied the anti-cancer activity of the synthesized thienopyrimidinone derivatives against MCF-7 and MCF-10A cancer cells. Furthermore, in vivo experiments showed that the synthesized compounds significantly reduced tumor growth up to the 8 th day of treatment in comparison to control animal models. Additionally, the synthesized derivatives showed potential inhibitory effects against pim-1 kinase activities.

A series of 16-(α-alkoxyalkane)-17-hydrazino-estra-1(10),2,4-trien[17,16-c]-3-ol ( 3a - l ) and estra-1(10),2,4-trien-[17,16-c]pyrazoline-3-ol derivatives ( 4a - d ) were synthesized from corresponding arylidines 2a,b which was prepared from estrone 1 as starting material. Condensation of 1 with aldehydes gave the corresponding arylidine derivatives 2 a,b which were treated with hydrazine derivatives in alcohols to give the corresponding derivatives 3a - l , respectively. Additionally, treatment of 2 a,b with methyl- or phenylhydrazine in ethanolic potassium hydroxide afforded the corresponding N-substituted pyrazoline derivatives 4a - d , respectively. All these derivatives showed potent anti-ovarian cancer both in vitro and in vivo . The mechanism of anti-ovarian cancer was suggested to process via topoisomerase II and V600E BRAF inhibition., Competing Interests: The authors declare no conflict of interest.

In this work, we demonstrated proof-of-concept for the use of ion-selective electrodes (ISEs) as a promising tool for the assessment of total antioxidant capacity (TAC). Novel membrane sensors for 2,6-dichlorophenolindophenolate (DCPIP) ions were prepared and characterized. The sensors membranes were based on the use of either Cu II -neocuproin/2,6-dichlorophenolindo-phenolate ([Cu(Neocup) 2 ][DCPIP] 2 ) (sensor I), or methylene blue/2,6-dichlorophenolindophenolate (MB/DCPIP) (sensor II) ion association complexes in a plasticized PVC matrix. The sensors revealed significantly enhanced response towards DCPIP ions over the concentration range 5.13 × 10 -5 -1.0 × 10 -2 and 5.15 × 10 -5 -1.0 × 10 -2 M at pH 7 with detection limits of 6.3 and 9.2 µg/mL with near-Nernstian slope of -56.2±1.7 and -51.6±2 mV/decade for sensors I and II, respectively. The effects of plasticizers and various foreign common ions were also tested. The sensors showed enhanced selectivity towards DCPIP over many other phenolic and inorganic ions. Long life span, high potential stability, high reproducibility, and fast response were also observed. Method validation was also verified by measuring the detection limit, linearity range, accuracy, precision, repeatability and between-day-variability. The sensors were introduced for direct determination of TAC in fresh and canned juice samples collected from local markets. The obtained results agreed fairly well with the data obtained by the standard method., Competing Interests: The authors declare no conflict of interest.

A series of estrone derivatives 3 ⁻ 8 was designed and synthesized using estrone arylmethylenes 2a , b as starting materials and their structures were confirmed by different spectral data and elemental analyses. All the newly synthesized compounds exhibited potent in vitro and in vivo cytotoxic activities against breast cancer cell lines. In addition, all compounds were subjected to in vitro and in vivo inhibition assays for EGFR and VEGFR-2 kinases as well as p53 ubiquitination activity to obtain more details about their mechanism of action. Based on the promising results, a molecular docking study was investigated for the most representative compound 5a against the two targets, EGFR and VEGFR-2 kinases, to assess its binding affinity, hoping to rationalize and obtain potent anticancer agents in the future.

Background & Objective: A series of novel derivatives possessing the thiophene moiety were synthesized using ethyl 5'-amino-2,3'-bithiophene-4'-carboxylate as the starting material., Methods: The new synthesized derivatives were screened as lactate dehydrogenase (LDH) inhibitors. LDH plays an important role in glucose metabolism in cancer cells and can affect tumor genesis and metastasis., Results: 3-Substituted p-tolylthieno[2,3-d]pyrimidin-4(3H)-ones 4 were the most potent inhibitors in this study compared to Galloflavin reference drug., Conclusion: Molecular docking studies on the Human Lactate Dehydrogenase active site were carried out on the synthesized compounds and the MolDock scores ranged between -127 to -171., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

A series of macrocyclic pyrido-pentapeptide candidates 2 ⁻ 6 were synthesized by using N , N -bis-[1-carboxy-2-(benzyl)]-2,6-(diaminocarbonyl)pyridine 1a , b as starting material. Structures of the newly synthesized compounds were established by IR, ¹H and 13 C-NMR, and MS spectral data and elemental analysis. The in-vitro cytotoxicity activity was investigated for all compounds against MCF-7 and HepG-2 cell lines and the majority of the compounds showed potent anticancer activity against the tested cell lines in comparison with the reference drugs. Out of the macrocyclic pyrido-pentapeptide based compounds, 5c showed encouraging inhibitory activity on MCF-7 and HepG-2 cell lines with IC 50 values 9.41 ± 1.25 and 7.53 ± 1.33 μM, respectively. Interestingly, 5c also demonstrated multitarget profile and excellent inhibitory activity towards VEGFR-2, CDK-2 and PDGFRβ kinases. Furthermore, molecular modeling studies of the compound 5c revealed its possible binding modes into the active sites of those kinases.

A series of estrone derivatives, 2 ⁻ 4 , were synthesized from the corresponding arylidine estrone, 2a , b , as starting materials, which were prepared by condensation of estrone (3-hydroxy-estran-17-one, 1) with 4-bromobenzaldehyde and thiophene-2-aldehyde. Treating of 2a , b with hydrazine derivatives in acetic acid or propionic acid afforded pyrazoline derivatives, 3a ⁻ f and 4a ⁻ f , respectively. Furthermore, results proved the superiority of thienyl derivatives over 4-bromophenol derivatives in terms of cytotoxic effects on MCF-7 cancer cells. In vivo xenograft breast cancer animal model experiments revealed that the synthesized derivatives can be used for decreasing tumor volume, while the most potent derivative ( 4f ) decreased the development of tumor volume by about 87.0% after 12 days.

Background: In this study, synthesis, molecular docking and anticancer screening of new series of substituted heterocycles with trimethoxy phenyl scaffold as Combretastatin analogues were described. Substituted pyridines were synthesized via the reaction of (E)-3-(dimethylamino)-1-(3,4,5- trimethoxyphenyl)prop-2-en-1-one (2) with active methylene reagents. Substituted pyrimidines were prepared by the reaction of the enaminone (2) with heterocyclic amines and 6-amino thiouracil. Furthermore, a series of pyrazoles substituted with trimethoxyphenyl scaffold were prepared by the reaction of the enaminone 2, with selected examples of hydrazonoyl halides., Conclusion: The cytotoxic effect of the newly compounds was evaluated against HePG-2, HCT-116, MCF-7 and PC3 cancer cell lines. Among the new products, compounds 2, 3, 7 and 10 were found to exhibit promising results as anticancer agents. The IC50 values of 2, 3 and 7 were 54.6, 77.4 and 47.4 on PC3 respectively. Also, compound 2 had IC50 28.06 on MCF7. Moreover, the selectivity index indicated that compounds 2 and 3 are safe., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

In this work, twenty-one thiopyrimidine (1-21) candidates containing a pyrane, pyrazoline and thiazolopyrimidine ring screened for their ED50 and 5α-reductase inhibitors comparable to that of Anastrozole as positive drug. Some of the tested product showed moderate 5α-reductase inhibitors with lower toxicity. The detailed ED 50 and 5α-reductase inhibitor activities of the synthesized compounds were studied.