Potentiometric PVC-Membrane-Based Sensor for Dimethylamine Assessment Using A Molecularly Imprinted Polymer as A Sensory Recognition Element.

A new simple potentiometric sensor is developed and presented for sensitive and selective monitoring of dimethylamine (DMA). The sensor incorporates a molecularly imprinted polymer, with a pre-defined specific cavity suitable to accommodate DMA. The molecularly imprinted polymer (MIP) particles were dispersed in an aplasticized poly(vinyl chloride) matrix. The MIP is synthesized by using a template molecule (DMA), a functional monomer (acrylamide, AM), cross-linker (ethylene glycol dimethacrylate, EGDMA) and initiating reagent (benzoylperoxide, BPO). Using Trizma buffer solution (5 mmol L-1, pH 7.1), the sensor exhibits a rapid, stable and linear response for 1.0 × 10-5 to 1.0 × 10-2 mol L-1 DMA+ with a calibration slope of 51.3 ± 0.3 mV decade-1, and a detection limit of 4.6 × 10-6 mol L-1 (0.37 µg mL-1). The electrode exhibited a short response time (10 s) and stable potential readings (± 0.5 mV) for more than 2 months. Potentiometric selectivity measurements of the sensor reveal negligible interferences from most common aliphatic and aromatic amines. High concentration levels (100-fold excess) of many inorganic cations do not interfere. The sensor is successfully used for quantification of low levels of DMA down to 0.5 µg mL-1. Verification of the presented method was carried out after measuring the detection limit, working linearity range, ruggedness of the method, accuracy, precision, repeatability and reproducibility. Under flow-through conditions, the proposed sensor in its tubular form is prepared and introduced in a two-channel flow injection setup for hydrodynamic determination of DMA. The sampling rate is 50-55 samples h-1. The sensor is used to determine DMA in different soil samples with an accuracy range of 97.0-102.8%.

Single-Piece All-Solid-State Potential Ion-Selective Electrodes Integrated with Molecularly Imprinted Polymers (MIPs) for Neutral 2,4-Dichlorophenol Assessment.

A novel single-piece all-solid-state ion-selective electrode (SC/ISE) based on carbon-screen printed is introduced. Polyaniline (PANI) is dissolved in a membrane cocktail that contains the same components used for making a conventional ion-selective polyvinyl chloride (PVC) matrix membrane. The membrane, having the PANI, is directly drop-casted on a carbon substrate (screen-printed-carbon electrode). PANI was added to act as an intermediary between the substrate and the membrane for the charge transfer process. Under non-equilibrium sensing mechanism, the sensors revealed high sensitivity towards 2,4-dichlorophenol (DCP) over the linearity range 0.47 to 13 µM and a detection limit 0.13 µm. The selectivity was measured by the modified separate solution method (MSSM) and showed good selectivity towards 2,4-DCP over the most commonly studied ions. All measurements were done in 30 mm Tris buffer solution at a pH 5.0. Using constant-current chronopotentiometry, the potential drift for the proposed electrodes was checked. Improvement in the potential stability of the SPE was observed after the addition of PANI in the sensing membrane as compared to the corresponding coated-wire electrode (membrane without PANI). The applicability of the sensor has been checked by measuring 2,4-DCP in different water samples and the results were compared with the standard HPLC method.

Tailor-Made Specific Recognition of Cyromazine Pesticide Integrated in a Potentiometric Strip Cell for Environmental and Food Analysis.

Screen-printed ion-selective electrodes were designed and characterized for the assessment of cyromazine (CYR) pesticide. A novel approach is to design tailor-made specific recognition sites in polymeric membranes using molecularly imprinted polymers for cyromazine (CR) determination (sensor I). Another sensor (sensor II) is the plasticized PVC membrane incorporating cyromazine/tetraphenyl borate ion association complex. The charge-transfer resistance and water layer reached its minimal by incorporating Polyaniline (PANI) solid-contact ISE. The designed electrodes demonstrated Nernstain response over a linear range 1.0 × 10-2-5.2 × 10-6 and 1.0 × 10-2-5.7 × 10-5 M with a detection limit 2.2 × 10-6 and 8.1 × 10-6 M for sensors I and II, respectively. The obtained slopes were 28.1 ± 2.1 (r2 = 0.9999) and 36.4 ± 1.6 (r2 = 0.9991) mV/decade, respectively. The results showed that the proposed electrodes have a fast and stable response, good reproducibility, and applicability for direct measurement of CYR content in commercial pesticide preparations and soil samples sprayed with CYR pesticide. The results obtained from the proposed method are fairly in accordance with those using the standard official method.

Improved Solid-Contact Nitrate Ion Selective Electrodes Based on Multi-Walled Carbon Nanotubes (MWCNTs) as an Ion-to-Electron Transducer.

Possible improvement of the performance characteristics, reliability and selectivity of solid-contact nitrate ion-selective electrodes (ISE) (SC/NO3--ISE) is attained by the application of a nitron-nitrate (Nit+/NO3-) 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/NO3--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.

Kinase Inhibitory Activities and Molecular Docking of a Novel Series of Anticancer Pyrazole Derivatives.

A series of novel 1,3,4-triarylpyrazoles containing different heterocycles has been prepared, characterized and screened for their in vitro antiproliferative activity against HePG-2, MCF-7, PC-3, A-549 and HCT-116 cancer cell lines. The biological results revealed that compound 6 showed the highest anticancer activity so it was subjected to a kinase assay study where it reduced the activity of several protein kinases including AKT1, AKT2, BRAF V600E, EGFR, p38α and PDGFRß at 100 µM using the radiometric or ADP-Glo assay method. Molecular docking simulation supported the initial kinase assay and suggested a common mode of interaction at the ATP-binding sites of these kinases, which demonstrates that compound 6 is a potential agent for cancer therapy deserving further research.

Anticancer evaluation and molecular modeling of multi-targeted kinase inhibitors based pyrido[2,3-d]pyrimidine scaffold.

An efficient synthesis of substituted pyrido[2,3-d]pyrimidines was carried out and evaluated for in vitro anticancer activity against five cancer cell lines, namely hepatic cancer (HepG-2), prostate cancer (PC-3), colon cancer (HCT-116), breast cancer (MCF-7), and lung cancer (A-549) cell lines. Regarding HepG-2, PC-3, HCT-116 cancer cell lines, 7-(4-chlorophenyl)-2-(3-methyl-5-oxo-2,3-dihydro-1H-pyrazol-1-yl)-5-(p-tolyl)- pyrido[2,3-d]pyrimidin-4(3H)-one (5a) exhibited strong, more potent anticancer (IC50: 0.3, 6.6 and 7 µM) relative to the standard doxorubicin (IC50: 0.6, 6.8 and 12.8 µM), respectively. Kinase inhibitory assessment of 5a showed promising inhibitory activity against three kinases namely PDGFR ß, EGFR, and CDK4/cyclin D1 at two concentrations 50 and 100 µM in single measurements. Further, a molecular docking study for compound 5a was performed to verify the binding mode towards the EGFR and CDK4/cyclin D1 kinases.

Synthesis and 2D-QSAR Study of Active Benzofuran-Based Vasodilators.

A new series of 2-alkyloxy-pyridine-3-carbonitrile-benzofuran hybrids (4a-x) was synthesized. All the new derivatives were examined via the standard technique for their vasodilation activity. Some of the investigated compounds exhibited a remarkable activity, with compounds 4w, 4e, 4r, 4s, 4f and 4g believed to be the most active hits in this study with IC50 values 0.223, 0.253, 0.254, 0.268, 0.267 and 0.275 mM, respectively, compared with amiodarone hydrochloride, the reference standard used (IC50 = 0.300 mM). CODESSA PRO was employed to obtain a statistically significant 2-Dimensional Quantitative Structure Activity Relationship (2D-QSAR) model describing the bioactivity of the newly synthesized analogs (N = 24, n = 4, R² = 0.816, R²cvOO = 0.731, R²cvMO = 0.772, F = 21.103, s² = 6.191 × 10-8).

Design and Synthesis of Novel Pyrazole-Substituted Different Nitrogenous Heterocyclic Ring Systems as Potential Anti-Inflammatory Agents.

With the aim of developing novel anti-inflammatory scaffolds, a new series of pyrazole-substituted various nitrogenous heterocyclic ring systems at C-4 position were synthesized through different chemical reactions and validated by means of spectral and elemental data. The new obtained compounds were investigated for their anti-inflammatory activity using the carrageenan-induced paw edema standard technique and revealed that, compound 6b showed increased potency with % inhibition of edema 85.23 ± 1.92 and 85.78 ± 0.99, respectively, higher than the standard reference drugs indomethacin and celebrex (72.99% and 83.76%). Molecular modeling studies were initiated herein to validate the attained pharmacological data and provide understandable evidence for the observed anti-inflammatory behavior.

Synthesis and Characterization of Some New N-Glycosides of Pyridine-2,6-bis-Carboxamides Derivatives.

A series of novel pyridine-bridged 2,6-bis-carboxamide N-ß-glycosides and Schiff's bases has been prepared starting from 2,6-bis-carboxamide pyridine hydrazide, which on treatment with appropriate monosaccharides, aromatic or heterocyclic aldehydes, and indoline-2,3-dione derivatives afforded the corresponding sugar hydrazones and pyridine-bridged 2,6-bis-carboxamide Schiff's bases.

Biological Validation of Novel Polysubstituted Pyrazole Candidates with in Vitro Anticancer Activities.

With the aim of developing novel antitumor scaffolds, a novel series of polysubstituted pyrazole derivatives linked to different nitrogenous heterocyclic ring systems at the C-4 position were synthesized through different chemical reactions and characterized by means of spectral and elemental analyses and their antiproliferative activity against 60 different human tumor cell lines was validated by the U.S. National Cancer Institute using a two stage process. The in vitro anticancer evaluation revealed that compound 9 showed increased potency toward most human tumor cell lines with GI50MG-MID = 3.59 µM, as compared to the standard drug sorafenib (GI50 MG-MID = 1.90 µM). At the same time, compounds 6a and 7 were selective against the HOP-92 cell line of non-small cell lung cancer with GI50 1.65 and 1.61 µM, respectively.

SYNTHESIS AND BIOLOGICAL EVALUATION OF SOME NOVEL FUSED THIAZOLO[3,2A]PYRIMIDINES AS POTENTIAL ANALGESIC AND ANTI-INFLAMMATORY AGENTS.

Some novel bicyclic thiazolopyrimidine derivatives bearing various substituents have been synthesized through one-pot three-component method. Structures of the target compounds were confirmed by elemental analysis and spectral data. Some selected members of the newly synthesized compounds were investigated for their analgesic and anti-inflammatory activities and revealed pronounced anti-inflammatory activity greater than that of indomethacin (reference drug).

Synthesis, docking and biological activities of novel hybrids celecoxib and anthraquinone analogs as potent cytotoxic agents.

Herein, novel hybrid compounds of celecoxib and 2-aminoanthraquinone derivatives have been synthesized using condensation reactions of celecoxib with 2-aminoanthraquinone derivatives or 2-aminoanthraquinon with celecoxib derivatives. Celecoxib was reacted with different acid chlorides, 2-chloroethylisocyanate and bis (2-chloroethyl) amine hydrochloride. These intermediates were then reacted with 2-aminoanthraquinone. Also the same different acid chlorides and 2-chloroethylisocyanate were reacted with 2-aminoanthraquinone and the resulting intermediates were reacted with celecoxib to give isomers for the previous compounds. The antitumor activities against hepatic carcinoma tumor cell line (HEPG2) have been investigated in vitro, and all these compounds showed promising activities, especially compound 3c, 7, and 12. Flexible docking studies involving AutoDock 4.2 was investigated to identify the potential binding affinities and the mode of interaction of the hybrid compounds into two protein tyrosine kinases namely, SRC (Pp60v-src) and platelet-derived growth factor receptor, PDGFR (c-Kit). The compounds in this study have a preferential affinity for the c-Kit PDGFR PTK over the non-receptor tyrosine kinase SRC (Pp60v-src).

Synthesis and biological evaluation of 2-thioxopyrimidin-4(1H)-one derivatives as potential non-nucleoside HIV-1 reverse transcriptase inhibitors.

A series of new 5-allyl-6-benzylpyrimidin-4(3H)-ones bearing different substituents at the C-2 position of the pyrimidine core have been synthesized and evaluated for their in vitro activities against human immunodeficiency virus type 1 (HIV-1) in the human T-lymphotropic type (MT-4 cell cultures). The majority of the title compounds showed moderate to good activities against HIV-1. Amongst them, 5-allyl-6-benzyl-2-(3-hydroxypropylthio)pyrimidin-4(3H)-one analogue 11c exhibited the most potent anti-HIV-1 activity (IC50 0.32 µM). The biological testing results clearly indicated that the substitution at C-2 position of the pyrimidine ring could increase the anti-HIV-1 reverse transcriptase (RT) activity.

Synthesis and evaluation of novel 6-(3,5-dimethylbenzyl)uracil analogs as potential anti-HIV-1 agents.

A novel series of uracil derivatives with a 3,5-dimethylbenzyl group at the C-6 position were synthesized and evaluated as non-nucleoside HIV-1 reverse transcriptase inhibitors. Purity of the compounds has been confirmed by TLC. Structures of these compounds were established on the basis of elemental analyses and spectral studies. Some of the tested compounds showed moderate to potent activities against wild-type HIV-1, and N-1 alkylated derivatives were highly active.

Analgesic and anticonvulsant activities of some newly synthesized trisubstituted pyridine derivatives.

A series of novel pyridine carbohydrazide derivatives were synthesized from the reaction of 2-chloro-6-hydrazino-isonicotinic acid hydrazide with selected active reagents. All prepared compounds were tested as analgesic and anticonvulsant agents. The pharmacological screening showed that many of these compounds have good activities comparable to those of valdecoxib and carbamazepine as reference drugs.

HIV-1 and HSV-1 virus activities of some new polycyclic nucleoside pyrene candidates.

In continuation of our previous work, a novel series of polycyclic derivatives 2-8 incorporated heterocyclic and sugar moieties were synthesized by using pyren-1-aldehyde (1) as starting material and their tested as antiviral activities. Initially, the toxicity of the compounds was assayed via the determination of their EC(50). Some of the synthesized compounds were tested as antiviral activity against HIV-1 and HSV-1. The structure of the new compounds was confirmed by using chemical and spectroscopic evidences. The detailed of synthesis, spectroscopic data, antiviral activities of the synthesized compounds were reported.

(E)-2-Cyano-N'-(1,2,3,4-tetra-hydro-naphthalen-1-yl-idene)acetohydrazide.

In the title compound, C(13)H(13)N(3)O, the tetra-hydro-benzene ring adopts a half-boat (envelope) conformation. The mean plane of the tetra-hydro-naphthalene ring system forms a dihedral angle of 9.56 (6)° with the mean plane of the cyano-acetohydrazide group. In the crystal, inversion dimers linked by pairs of N-H⋯O hydrogen bonds generate R(2) (2)(8) loops. The dimers are connected by C-H⋯N hydrogen bonds into a chain propagating along [101]. The crystal packing also features C-H⋯π inter-actions.

Synthesis and anti-inflammatory evaluation of new substituted 1-(3-chlorophenyl)-3-(4-methoxyphenyl)-1H-pyrazole derivatives.

A series of heterocyclic derivatives including 1,2,4-triazole-3(4H)-one (3a,b), 1H-pyrazol-5(4H)-one (4,5), 1H-pyrazol-4-carbonitrile (7), pyridine-3-carbonitrile (8, 9a,b), pyrimidine-5-carbonitrile (10a,b), methylpyrimidin-2(1H)-one or thione (11a,b), pyrimidine-5-carboxylate (12a,b), quinazolin-5(6H)-one (13a,b) and indeno [1,2-d] pyrimidin-5-one (14a,b) moieties conjugated with 1,3-disubstituted pyrazole moiety were synthesized on reaction with semicarbazide, thiosemicarbazide, 3-amino-5-oxo-2-pyrazoline, cyanoacetohydrazide, 2-acetyl thiophene, p-chloroacetophenone, urea, thiourea and 1,3-dicarbonyl compounds, respectively, by using 1-(3-chlorophenyl)-3-(4-methoxyphenyl)-1H-pyrazole-4-carboxaldehyde (2) as starting material. The structures of all the newly synthesized products have been established on the basis of analytical and spectral data. The anti-inflammatory screening showed that most of the obtained compounds were found to have significant anti-inflammatory activities with prostaglandin inhibition at a dose level of 2.5 and 5 mg/kg comparable to celecoxib as a reference control. The ulcer indices of all compounds are mainly in the safe level (UI = 2.10-4.27) except for compounds 9a and 14a, which were highly ulcerogenic.