In Vitro Evaluation and Bioinformatics Analysis of Schiff Bases Bearing Pyrazole Scaffold as Bioactive Agents: Antioxidant, Anti-Diabetic, Anti-Alzheimer, and Anti-Arthritic.

In continuation of our research programs for the discovery, production, and development of the pharmacological activities of molecules for various disease treatments, Schiff bases and pyrazole scaffold have a broad spectrum of activities in biological applications. In this context, this manuscript aims to evaluate and study Schiff base-pyrazole molecules as a new class of antioxidant (total antioxidant capacity, iron-reducing power, scavenging activity against DPPH, and ABTS radicals), anti-diabetic (α-amylase% inhibition), anti-Alzheimer's (acetylcholinesterase% inhibition), and anti-arthritic (protein denaturation% and proteinase enzyme% inhibitions) therapeutics. Therefore, the Schiff bases bearing pyrazole scaffold (22a, b and 23a, b) were designed and synthesized for evaluation of their antioxidant, anti-diabetic, anti-Alzheimer's, and anti-arthritic properties. The results for compound 22b demonstrated significant antioxidant, anti-diabetic (α-amylase% inhibition), and anti-Alzheimer's (ACE%) activities, while compound 23a demonstrated significant anti-arthritic activity. Prediction of in silico bioinformatics analysis (physicochemical properties, bioavailability radar, drug-likeness, and medicinal chemistry) of the target derivatives (22a, b and 23a, b) was performed. The molecular lipophilicity potential (MLP) of the derivatives 22a, b and 23a, b was measured to determine which parts of the surface are hydrophobic and which are hydrophilic. In addition, the molecular polar surface area (PSA) was measured to determine the polar surface area and the non-polar surface area of the derivatives 22a, b and 23a, b. This study could be useful to help pharmaceutical researchers discover a new series of potent agents that may act as an antioxidant, anti-diabetic, anti-Alzheimer, and anti-arthritic.

Investigations of Electronic, Structural, and In Silico Anticancer Potential of Persuasive Phytoestrogenic Isoflavene-Based Mannich Bases.

Isoflavenes have received the greatest research attention among the many groups of phytoestrogens. In this study, various isoflavene-based Mannich bases were selected for their theoretical studies. The purpose of this research was to discover the binding potential of all the designated Mannich bases acting as inhibitors against cancerous proteins EGFR, cMet, hTrkA, and HER2 (PDB codes: 5GTY, 3RHK, 6PL2, and 7JXH, respectively). For their virtual screening, DFT calculations and molecular docking studies were undertaken using in silico software. Docking studies predicted that ligands 5 and 15 exhibited the highest docking score by forming hydrogen bonds within the active pocket of protein 6PL2, ligands 1 and 15 both with protein 3RHK, and 7JXH, 12, and 17 with protein 5GTY. Rendering to the trends in polarizability and dipole moment, the energy gap values (0.2175 eV, 0.2106 eV) for the firm conformers of Mannich bases (1 and 4) replicate the increase in bioactivity and chemical reactivity. The energy gap values (0.2214 eV and 0.2172 eV) of benzoxazine-substituted isoflavene-based Mannich bases (9 and 10) reflect the increase in chemical potential due to the most stable conformational arrangements. The energy gap values (0.2188 eV and 0.2181 eV) of isoflavenes with tertiary amine-based Mannich bases (14 and 17) reflect the increase in chemical reactivity and bioactivity due to the most stable conformational arrangements. ADME was also employed to explore the pharmacokinetic properties of targeted moieties. This study revealed that these ligands have a strong potential to be used as drugs for cancer treatment.

Alleviative effects of pinostrobin against cadmium-induced renal toxicity in rats by reducing oxidative stress, apoptosis, inflammation, and mitochondrial dysfunction.

Introduction: Cadmium (Cd) is a highly toxic heavy metal that can be found everywhere in the environment and can have harmful effects on both human and animal health. Pinostrobin (PSB) is a bioactive natural flavonoid isolated from Boesenbergia rotunda with several pharmacological properties, such as antiinflammatory, anticancer, antioxidant, and antiviral. This investigation was intended to assess the therapeutic potential of PSB against Cd-induced kidney damage in rats. Methods: In total, 48 Sprague Dawley rats were divided into four groups: a control, a Cd (5 mg/kg), a Cd + PSB group (5 mg/kg Cd and 10 mg/kg PSB), and a PSB group (10 mg/kg) that received supplementation for 30 days. Results: Exposure to Cd led to a decrease in the activities of catalase (CAT), glutathione reductase (GSR), superoxide dismutase (SOD), and glutathione peroxidase (GSH-PX), whereas levels of reactive oxygen species (ROS) and malondialdehyde (MDA) increased. Cd exposure also caused a substantial increase in urea, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and creatinine levels. Moreover, a noticeable decline was noticed in creatinine clearance. Moreover, Cd exposure considerably increased the levels of inflammatory indices, including interleukin-1b (IL-1b), tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6), nuclear factor kappa-B (NF-kB), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) activity. Cd treatment decreased the expression of the antiapoptotic markers (Bcl-2) while increasing the expression of apoptotic markers (Bax and Caspase-3). Furthermore, Cd treatment substantially reduced the TCA cycle enzyme activity, such as alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, and isocitrate dehydrogenase. Moreover, mitochondrial electron transport chain enzymes, succinatedehydrogenase, NADH dehydrogenase, cytochrome c-oxidase, and coenzyme Q-cytochrome reductase activities were also decreased following Cd exposure. PSB administration substantially reduced the mitochondrial membrane potential while inducing significant histological damage. However, PSB treatment significantly reduced Cd-mediated renal damage in rats. Conclusion: Thus, the present investigation discovered that PSB has ameliorative potential against Cd-induced renal dysfunction in rats.

Anti-inflammatory activity of novel derivatives of pyrazolo [3,4d] pyridazine against digestive system inflammation.

The digestive system is exposed to severe inflammation as a result of taking some medications that have gastrointestinal side effects. Sixty Swiss-albino male mice were randomly distributed into six groups to treat inflammations of the colon, stomach, and small intestine caused by taking high doses of diclofenac (D), with two novel synthesized compounds, pyrazolo [3,4 d] pyridazine derivatives (Co1 and Co2). Myeloperoxidase enzyme activity was determined in the colon and small intestinal tissues. Serum contents of TNF-α, IL-22, IgG, and IgM were determined by ELISA. Histopathological examinations of the colon, small intestinal, and stomach tissues were microscopically analyzed. TNF-α, IL-22, and TNFSF11 gene expression were measured in the colon, intestinal, and spleen using qRT-PCR. Diclofenac caused surface columnar epithelial cell loss, focal necrosis of the gastric mucosa, inflammatory cell infiltration, and congested blood vessels in the stomach, colon, and small intestinal tissues. Co1 component was found to be better than Co2 component in reducing the focal necrosis of gastric mucosa and improving the histological structures of the stomach, colon, and small intestinal tissues. After 14 days, the activity of the myeloperoxidase enzyme was increased in group D and decreased in groups DCo1, DCo2, Co1, and Co2. Serum concentrations of TNF-α and IgG were increased, while IL-22 and IGM were reduced in the D, DCo1, and DCo2 groups compared with the Co1 and control groups. TNF-α gene was upregulated in the D group and downregulated in the Co1 group, while the IL-22 gene was downregulated in the D group and upregulated in the Co1 group compared with the control group. The CO1 component may be useful in reducing digestive system inflammation.

Exploring Antimicrobial Features for New Imidazo[4,5-b]pyridine Derivatives Based on Experimental and Theoretical Study.

5-bromopyridine-2,3-diamine reacted with benzaldehyde to afford the corresponding 6-Bromo-2-phenyl-3H-imidazo[4,5-b]pyridine (1). The reaction of the latter compound (1) with a series of halogenated derivatives under conditions of phase transfer catalysis solid-liquid (CTP) allows the isolation of the expected regioisomers compounds (2-8). The alkylation reaction of (1) gives, each time, two regioisomers, N3 and N4; in the case of ethyl bromoactate, the reaction gives, at the same time, the three N1, N3 and N4 regioisomers. The structures of synthesized compounds were elucidated on the basis of different spectral data (1H NMR, 13C NMR), X-Ray diffraction and theoretical study using the DFT method, and confirmed for each compound. Hirshfeld surface analysis was used to determine the intermolecular interactions responsible for the stabilization of the molecule. Density functional theory was used to optimize the compounds, and the HOMO-LUMO energy gap was calculated, which was used to examine the inter/intra molecular charge transfer. The molecular electrostatic potential map was calculated to investigate the reactive sites that were present in the molecule. In order to determine the potential mode of interactions with DHFR active sites, the three N1, N3 and N4 regioisomers were further subjected to molecular docking study. The results confirmed that these analogs adopted numerous important interactions, with the amino acid of the enzyme being targeted. Thus, the most docking efficient molecules, 2 and 4, were tested in vitro for their antibacterial activity against Gram-positive bacteria (Bacillus cereus) and Gram-negative bacteria (Escherichia coli). Gram-positive bacteria were more sensitive to the action of these compounds compared to the Gram-negative, which were much more resistant.

Nα-1, 3-Benzenedicarbonyl-Bis-(Amino Acid) and Dipeptide Candidates: Synthesis, Cytotoxic, Antimicrobial and Molecular Docking Investigation.

PURPOSE: The objective of our work was to prepare a potent and safe antimicrobial and anticancer agents, through synthesis of several peptides and examine their biological activities, namely as, cytotoxically potent and antimicrobial and antifungal agents. INTRODUCTION: Multidrug-resistant microbial strains have arisen against all antibiotics in clinical use. Infections caused by these bacteria threaten global public health and are associated with high mortality rates. METHODS: The main backbone structure for the novel synthesized linear peptide is Nα-1, 3-benzenedicarbonyl-bis-(Amino acids)-X, (3-11). A computational docking study against DNA gyrase was performed to formulate a mode of action of the small compounds as antimicrobial agents. RESULTS: The peptide-bearing methionine-ester (4) exhibited potent antimicrobial activity compared to the other synthesized compounds, while, peptide (8), which had methionine-hydrazide fragment was the most potent as antifungal agent against Aspergillus niger with 100% inhibition percent. Compounds (6 and 7) showed the highest potency against breast human tumor cell line "MCF-7" with 95.1% and 79.8% of cell inhibition, respectively. The nine compounds possessed weak to moderate antiproliferative effect over colon tumor cell line. The docking results suggest good fitting through different hydrogen bond interactions with the protein residues. In silico ADMET study also evaluated and suggested that these compounds had promising oral bioavailability features. CONCLUSION: The tested compounds need further modification to have significant antimicrobial and antitumor efficacy compared to the reference drugs.

An all-solid-state potentiometric sensor modified with multi-walled carbon nanotubes (MWCNTs) for silicate assessment and water-quality testing.

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+[SiO3]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 SO42-, NO3-, CH3COO-, CO32-, Cl-, S2-, and PO43-. 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.

Correction: Integrated all-solid-state sulfite sensors modified with two different ion-to-electron transducers: rapid assessment of sulfite in beverages.

[This corrects the article DOI: 10.1039/D0RA09903A.].

Integrated all-solid-state sulfite sensors modified with two different ion-to-electron transducers: rapid assessment of sulfite in beverages.

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.

Solid-State Membrane Sensors Based on Man-Tailored Biomimetic Receptors for Selective Recognition of Isoproturon and Diuron Herbicides.

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 (r2 = 0.997) and 57.2 ± 0.3 (r2 = 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.

Synthesis, Docking, Computational Studies, and Antimicrobial Evaluations of New Dipeptide Derivatives Based on Nicotinoylglycylglycine Hydrazide.

Within a series of dipeptide derivatives (5-11), compound 4 was refluxed with d-glucose, d-xylose, acetylacetone, diethylmalonate, carbon disulfide, ethyl cyanoacetate, and ethyl acetoacetate which yielded 5-11, respectively. The candidates 5-11 were characterized and their biological activities were evaluated where they showed different anti-microbial inhibitory activities based on the type of pathogenic microorganisms. Moreover, to understand modes of binding, molecular docking was used of Nicotinoylglycine derivatives with the active site of the penicillin-binding protein 3 (PBP3) and sterol 14-alpha demethylase's (CYP51), and the results, which were achieved via covalent and non-covalent docking, were harmonized with the biological activity results. Therefore, it was extrapolated that compounds 4, 7, 8, 9, and 10 had good potential to inhibit sterol 14-alpha demethylase and penicillin-binding protein 3; consequently, these compounds are possibly suitable for the development of a novel antibacterial and antifungal therapeutic drug. In addition, in silico properties of absorption, distribution, metabolism, and excretion (ADME) indicated drug likeness with low to very low oral absorption in most compounds, and undefined blood-brain barrier permeability in all compounds. Furthermore, toxicity (TOPKAT) prediction showed probability values for all carcinogenicity models were medium to pretty low for all compounds.

Synthesis of Novel Sulfamethaoxazole 4-Thiazolidinone Hybrids and Their Biological Evaluation.

A search for potent antitubercular agents prompted us to design and synthesize sulfamethaoxazole incorporated 4-thiazolidinone hybrids (7a-l) by using a cyclocondensation reaction between 4-amino-N-(5-methylisoxazol-3-yl)benzenesulfonamide (4), aryl aldehyde (5a-l), and mercapto acetic acid (6) resulting in good to excellent yields. All the newly synthesized 4-thiazolidinone derivatives were screened for their in vitro antitubercular activity against M. Bovis BCG and M. tuberculosis H37Ra (MTB) strains. The compounds 7d, 7g, 7i, 7k, and 7l revealed promising antimycobacterial activity against M. Bovis and MTB strains with IC90 values in the range of 0.058-0.22 and 0.43-5.31 µg/mL, respectively. The most active compounds were also evaluated for their cytotoxicity against MCF-7, HCT 116, and A549 cell lines and were found to be non-cytotoxic. Moreover, the synthesized compounds were also analyzed for ADME (absorption, distribution, metabolism, and excretion) properties and showed potential as good oral drug candidates.

Novel heterocyclic hybrids of pyrazole targeting dihydrofolate reductase: design, biological evaluation and in silico studies.

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-1H-pyrazol-4(5H)-ylidene) hydrazine 3a or 6-amino-7-cyano-3-methyl-5H-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 IC50 values 0.11 ± 1.05 and 0.09 ± 0.91 µM, in comparison with methotrexate (IC50 = 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.

A New Validated Potentiometric Method for Sulfite Assay in Beverages Using Cobalt(II) Phthalocyanine as a Sensory Recognition Element.

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.

CuFe2O4/Polyaniline (PANI) Nanocomposite for the Hazard Mercuric Ion Removal: Synthesis, Characterization, and Adsorption Properties Study.

Copper ferrite nano-particles (CuFe2O4) were synthesized, characterized, modified with polyaniline to form CuFe2O4/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 CuFe2O4 nano-particles (NPs) in presence and absence of PANI nano-composite. The synthesized CuFe2O4NPs were of spherical shape with an average size of 10.8 nm. XRD analysis displayed crystal peaks for CuFe2O4NPs and amorphous peaks CuFe2O4/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 CuFe2O4 and CuFe2O4/PANI, respectively. The adsorption processes were fitted to Langmuir isotherms. The adsorption behavior of CuFe2O4@PANI composite towards Hg2+ 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 CuFe2O4@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 CuFe2O4 toward the adsorption of mercury from aqueous solutions.

Validation of a Novel Potentiometric Method Based on a Polymeric PVC Membrane Sensor Integrated with Tailored Receptors for the Antileukemia Drug Cytarabine.

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.

Solid-Contact Potentiometric Sensors Based on Stimulus-Responsive Imprinted Polymers for Reversible Detection of Neutral Dopamine.

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.

Synthesis, Characterization, and Anti-diabetic Activity of Some Novel Vanadium-Folate-Amino Acid Materials.

A new six intraperitoneal injections insulin-mimetic vanadyl(IV) compounds [(VO)(FA)(AAn)] (where n = 1-6: AA1 = isoleucine, AA2 = threonine, AA3 = proline, AA4 = phenylalanine, AA5 = lysine, and AA6 = glutamine) were synthesized by the chemical reactions between folic acid (FA), VOSO4, and amino acids (AAn) with equal molar ratio 1:1:1 in neutralized media. These complexes were characterized by elemental analysis and estimation of vanadyl(IV) metal ions. The thermal stability behavior of these complexes was studied by TG-DTG-DTA analyses. The structures of these complexes were elucidated by spectroscopic methods like infrared, electron spin resonance (ESR), and solid reflectance spectroscopes. The powder X-ray diffraction (XRD) study suggested the crystalline nature of the complexes. Magnetic moments and electronic spectra revealed the square-pyramid geometrical structure of the complexes. The conductivity results refereed that all synthesized vanadyl(IV) complexes were of a non-electrolyte behavior. The infrared spectra assignments of these complexes revealed that the FAH2 and AAn chelates act as a bidentate ligation. The chelation towards vanadyl (IV) ions existed via deprotonation of one of the carboxylic groups of FAH2 drug ligand, and so amino acids act as bidentate ligands via N-amino and O-carboxylate groups. Both scanning and transmission electron microscope (SEM and TEM) techniques were used to investigate the surface morphology. The main task of this research is the aim of designing a new insulin alternative antidiabetic drug agent. The antidiabetic efficiency of these complexes was evaluated in streptozotocin-induced diabetic male albino rats. Liver and kidney functions, insulin and blood glucose levels, lipid profile, and superoxide dismutase antioxidant (SOD) are verified identifiers for the efficiency of VO(IV)/FA/AAn system compounds as antidiabetic drug agents.

Biological Evaluation and Molecular Docking with In Silico Physicochemical, Pharmacokinetic and Toxicity Prediction of Pyrazolo[1,5-a]pyrimidines.

Pyrazolo[1,5-a]pyrimidines 5a-c, 9a-c and 13a-i were synthesized for evaluation of their in vitro antimicrobial properties against some microorganisms and their immunomodulatory activity. The biological activities of pyrazolo[1,5-a]pyrimidines showed that the pyrazolo[1,5-a]pyrimidines (5c, 9a, 9c, 13a, 13c, 13d, 13e and 13h) displayed promising antimicrobial and immunomodulatory activities. Studying the in silico predicted physicochemical, pharmacokinetic, ADMET and drug-likeness properties for the pyrazolo[1,5-a]pyrimidines 5a-c, 9a-c and 13a-i confirmed that most of the compounds (i) were within the range set by Lipinski's rule of five, (ii) show higher gastrointestinal absorption and inhibition of some CYP isoforms, and (iii) have a carcinogenicity test that was predicted as negative and hERG test that presented medium risk. Moreover, the molecular docking study demonstrated that the compounds 5c, 9a, 9c, 13a, 13c, 13d, 13e and 13h are potent inhibitors of 14-alpha demethylase, transpeptidase and alkaline phosphatase enzymes. This study could be valuable in the discovery of a new series of drugs.

Novel sulindac derivatives: synthesis, characterisation, evaluation of antioxidant, analgesic, anti-inflammatory, ulcerogenic and COX-2 inhibition activity.

A new series of N'-(substituted phenyl)-2-(1-(4-(methylsulfinyl) benzylidene)-5-fluoro-2-methyl-1H-inden-3-yl) acetohydrazide derivatives (1 - 25) were prepared in good yields in an efficient manner. All the compounds were fully characterised by the elemental analysis and spectral data. Synthesised compounds were evaluated for antioxidant activity by DPPH method. Compounds 7 (R = 3-methoxyphenyl), 3 (R = 4-dimethylaminophenyl) and 23 (R = 2,4,5-trimethoxy phenyl) substitutions were found to be having highly potent antioxidant activity. Compound 3, with para dimethylaminophenyl substitution was found to be having highest antioxidant activity. It was further evaluated in vivo for various analgesic, anti-inflammatory, ulcerogenic and COX-2 inhibitory activity in different animal models. Lead compound 3 was found to be significant anti-inflammatory and analgesic agent. It was also evaluated for ulcerogenic activity and demonstrated significant ulcerogenic reduction activity in ethanol and indomethacin model. The LD50 of compound 3 was found to be 131 mg/kg. The animals treated with compound 3 prior to cisplatin treatment resulted in a significant reduction in COX-2 protein expression when compared to cisplatin-treated group. Sulindac derivative with para dimethylaminophenyl substitution was found to be the most potent antioxidant, anti-inflammatory and analgesic agent as well as with significant gastric sparing activity as compared to standard drug sulindac. Compound 3 significantly downregulated liver tissue COX-2 gene expression.