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A novel spirooxindole‐pyrrolidine clubbed thiochromene and pyrazole motifs were synthesized by [3+2] cycloaddition (32CA) reactions in one step process starting from the ethylene‐based thiochromene and pyrazole scaffolds with the secondary amino‐acids and substituted isatins in high yield. The 32CA reaction of AY 10 with ethylene derivative 6 has also been studied with Molecular Electron Density Theory. The high nucleophilic character of AY 10, N = 4.39 eV, allows explaining that the most favorable TS‐on is 13.9 kcal mol−1 below the separated reagent. This 32CA, which takes place through a non‐concerted one‐step mechanism, presents a total ortho regio‐ and endo stereoselectivity, which is controlled by the formation of two intramolecular H...O hydrogen bonds. The design of spirooxindole‐pyrrolidines engrafted thiochromene and pyrazole was tested for alpha‐amylase inhibition and show a high efficacy in nanoscale range of reactivity. The key interaction between the most active hybrids and the receptor was studied by molecular docking. The physiochemical properties of the designed spirooxindole‐pyrrolidines were carried out by in silico ADMET prediction. The newly synthesized most potent hybrid could be considered as a lead compound for drug discovery development for type 2 diabetes mellitus (T2DM). [ABSTRACT FROM AUTHOR]

Herein, we present an experimental and theoretical drug–drug interaction study between nitazoxanide (NTZ) and azithromycin (AZT) in an aqueous solution. Interaction was studied by using UV/Vis, fluorescence, attenuated total reflectance‐fourier transform infrared (ATR‐FTIR), and circular dichroism (CD) spectroscopy, while molecular docking studies were performed to establish the interaction computationally. A bright yellow color was observed when the two drugs interacted, giving a hyperchromic band at 420 nm. The rate of absorbance was linearly increased by increasing drug concentrations and in a time‐dependent manner. Stability of the interaction complex (i.e., NTZ: AZT) was measured at variable temperatures (25–80°C), pH (5.0–10.0) and ionic strength (0.05–2.0 M NaCl), and not only proved stable but also retained antimicrobial potential with reduced cellular toxicity. Mole ratio and Job's method of continuous variations were used to establish the binding stoichiometry and found to be 2:1. The calculated binding constant (kb = 8,400 M−1) and Gibb's free energy (ΔG° = −22.4 KJ/mol) also suggested an energetically favorable interaction. FTIR spectra of NTZ: AZT complex in comparison with two drugs alone revealed significant interaction which was nicely complemented by molecular docking studies. Interaction was also successfully demonstrated in presence of carrier protein HSA and by spiking the two drugs in real samples of human plasma and urine. [ABSTRACT FROM AUTHOR]

This paper proposes a new framework for the planning of both distributed generators (DGs) and electric vehicle charging stations (EVCSs). The proposed method efficiently produces a unified solution for the joint planning of DGs and EVCSs for both grid‐connected and islanded scenarios. The problem is formulated as a novel two‐stage planning problem. The first stage determines the locations and sizes of the DGs with locations of EVCSs in grid‐connected scenario, whereas the second stage planning identifies the optimal islands under the islanded microgrid scenario. A non‐dominated sorting genetic algorithm (NSGA‐II) is applied to solve the first stage planning problem; in this stage, the algorithm minimizes two objective functions: the system‐losses and total cost. In the second stage, another single objective optimization problem is designed which minimizes supply voltage variations to find optimal islands for the DGs and EVCSs to ensure a secure supply of power for EVs. The proposed framework is implemented on the IEEE 33‐bus system and verified with four test cases. The results demonstrate the effectiveness of the proposed method and show that the sizes and locations of DGs, and locations of EVCSs are adequate for both grid‐connected and islanded microgrids. [ABSTRACT FROM AUTHOR]

POPDC1 also known as BVES, is a highly conserved transmembrane protein, important for striated muscle function and homeostasis. Pathogenic variants in the POPDC1 gene are associated with limb‐girdle muscular dystrophy type 25 (LGMDR25). In the present study, we performed trio‐whole exome sequencing (WES) followed by Sanger sequencing on a single family having LGMD clinical features. Protein modeling of all POPDC1 missense variants (POPDC1Pro134Leu, POPDC1Ile193Ser, and POPDC1Ser201Phe) associated with LGMDR25 were performed using Molecular Dynamics (MD) simulation. We identified a homozygous missense variant (c.401C>T; p.Pro134Leu) in the POPDC1 gene. Altered 3D structure, disruptive fluctuation, less compactness, and instability were observed in all the three variants of POPDC1 protein models. In comparison, POPDC1Ser201Phe protein dynamics were more unstable than other variants. Functional study of newly identified variant would add key answers to underlying mechanisms of the disease. [ABSTRACT FROM AUTHOR]

One of the challenging issues in the realization of medium‐voltage DC (MVDC) distribution system is high‐speed protection scheme design against quickly rising short circuit fault‐DC current. This paper proposes a high‐speed protection scheme based on the processing of energy signals through mathematical morphology (MM). The voltage and current signals measured at a distribution line section (DLS) are used to obtain the energy signal. The proposed scheme develops a modified MM‐based filter to extract the transient information in the energy signal rapidly and distinctly in the form of positive/negative polarity. The polarity detection of any disturbance in the analysed energy signal indicates the occurrence of a sudden disturbance in the system. The sudden disturbance occurrence confirmation triggers the faulty DLS identification and classification algorithms of the proposed scheme. The faulty DLS identification and classification algorithms are based on the detected polarities of the energy signal. The protection scheme requires low bandwidth communication. The proposed protection scheme is evaluated by using a ±2.5 kV radial distribution network containing 4 feeders under different fault conditions in MATLAB/SIMULINK software. Simulation results verify that the proposed scheme can isolate the faulty portion within a few milliseconds after fault inception under a variety of fault cases. [ABSTRACT FROM AUTHOR]

About 19 spirooxindole analogs 8 a–s engrafted with pyrazole scaffolds were designed and constructed via [3+2] cycloaddition reaction (32CA) approach. The synthesized spirooxindole analogs was screened for anti‐cholinesterase against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) and antioxidant potentials against DPPH. The compounds 8 h and 8 i showed the strongest acetylcholine esterase (AChE) and butyrylcholinesterase (BChE) inhibition with IC50 values of 30 μg/mL respectively. The highest anti‐oxidant potential was demonstrated by compounds 8 p with IC50 values of 240 μg/mL, respectively. Molecular docking was used to study their interaction with the active site of enzymes. [ABSTRACT FROM AUTHOR]

Urease plays a significant role in the pathogenesis of urolithiasis pyelonephritis, urinary catheter encrustation, hepatic coma, hepatic encephalopathy, and peptic acid duodenal ulcers. Salvinia molesta was explored to identify new bioactive compounds with particular emphasis on urease inhibitors. The aqueous methanol extract was fractionated using solvents of increasing polarity. A series of column chromatography and later HPLC were performed on butanol extract. The structures of the resulting pure compounds were resolved using NMR (1D and 2D), infrared, and mass spectroscopy. The novel isolate was evaluated for antioxidant activity (using DPPH, superoxide anion radical scavenging, oxidative burst, and Fe+2 chelation assays), anti‐glycation behavior, anticancer activity, carbonic anhydrase inhibition, phosphodiesterase inhibition, and urease inhibition. One new glucopyranose derivative 6′‐O‐(3,4‐dihydroxybenzoyl)‐4′‐O‐(4‐hydroxybenzoyl)‐α/β‐D‐glucopyranoside (1) and four known glycosides were identified. Glycoside 1 demonstrated promising antioxidant potential with IC50 values of 48.2 ± 0.3, 60.3 ± 0.6, and 42.1 ± 1.8 μM against DPPH, superoxide radical, and oxidative burst, respectively. Its IC50 in the Jack bean urease inhibition assay was 99.1 ± 0.8 μM. The mechanism‐based kinetic studies presented that compound 1 is a mixed‐type inhibitor of urease with a Ki value of 91.8 ± 0.1 μM. Finally, molecular dynamic simulations exploring the binding mode of compound 1 with urease provided quantitative agreement between estimated binding free energies and the experimental results. The studies corroborate the use of compound 1 as a lead for QSAR studies as an antioxidant and urease inhibitor. Moreover, it needs to be further evaluated through the animal model, that is, in vivo or tissue culture‐based ex‐vivo studies, to establish their therapeutic potential against oxidative stress phosphodiesterase‐II and urease‐induced pathologies. [ABSTRACT FROM AUTHOR]

Twenty‐three benzoxazole derivatives were prepared through two‐step reaction strategy. The precursor, 2‐mercapto benzoxazole was synthesized by reacting 2‐amino phenol with carbon disulfide in the presence of potassium hydroxide. Then, 2‐mercapto benzoxazole was further reacted with substituted phenacyl/benzyl bromide to afford a range of substituted 2‐mercapto benzoxazole analogs. All compounds were characterized by different spectroscopic techniques including mass spectrometry and nuclear magnetic resonance spectroscopy, and investigated against urease enzyme. All analogs revealed good to moderate urease inhibition, ranging from IC50 = 17.50±0.10 to 42.50±0.44 μM. Few derivatives showed superior activity than thiourea (IC50=21.50±0.47 μM), standard inhibitor of urease enzyme. Structure‐activity relationship (SAR) revealed the crucial participation of various structural features in the inhibitory process. Compounds bearing methoxy and halogen substituents were found to show more potency as compared with other molecules. Molecular docking showed various interesting interactions established by molecules (ligand) with the active pocket of urease enzyme. [ABSTRACT FROM AUTHOR]

In this study, we investigated surface and biological properties of Ag–Sr‐doped mesoporous bioactive glass nanoparticle (Ag–Sr MBGN) loaded chitosan/gelatin coatings deposited by electrophoretic deposition (EPD) on 316L stainless steel. The EPD parameters, that is, deposition time, applied voltage, and distance between the electrodes was optimized by the Taguchi design of experiment (DoE) approach. Scanning electron microscopy (SEM) images illustrated the spherical morphology of the synthesized Ag–Sr MBGNs with the mean particle size of 160 ± 20 nm. Energy‐dispersive X‐ray (EDX) spectroscopy results confirmed the presence of Ag and Sr in the synthesized MBGNs. Optimum EPD parameters determined by DoE approach were 5 g/L of Ag–Sr MBGNs, deposition time of 5 min, and applied voltage of 30 V. SEM images confirmed that the coatings were fairly homogenous. Fourier‐transform infrared spectroscopy and EDX results confirmed the presence of chitosan, gelatin, and Ag–Sr MBGNs in the coatings. Chitosan/gelatin/Ag–Sr MBGN composite coatings exhibited suitable wettability for the protein attachment and proliferation of osteoblast cells. The composite coatings exhibited suitable adhesion strength with the substrate. The coatings developed HA crystals upon immersion in simulated body fluid. The results of the turbidity test confirmed that the coatings are antibacterial to the Escherichia coli cells. [ABSTRACT FROM AUTHOR]

In this study, zein/45S5 bioactive glass (BG) coatings were deposited via electrophoretic deposition (EPD) on pretreated pure magnesium (Mg) substrates to control the rapid degradation of magnesium and to improve the bioactive properties of Mg implants. The EPD parameters were first optimized on stainless steel (SS), and then, the optimum EPD parameters were applied to obtain zein/BG composite coatings on Mg substrates. The kinetics of the EPD process was studied by plotting the graph between current density and deposition time at fixed applied voltage. The morphology and chemical composition (qualitatively) of the obtained coatings were studied by scanning electron microscopy (SEM) and Fourier‐transformed infrared spectroscopy (FTIR), respectively. SEM and FTIR results showed that both zein and BG were successfully deposited, and a homogeneous film of zein/BG was formed on the surface of the substrate. The contact angle measurements confirmed that the zein/BG coatings are suitable for the initial protein attachment. [ABSTRACT FROM AUTHOR]

A series of 3,5‐disubstituted‐tetrahydro‐thiadiazine‐2‐thione (1‐16) have been synthesized, characterized by elemental analysis, infrared (IR), UV‐visible, 1H NMR, 13C NMR, and MS spectroscopic techniques, and screened against jack bean urease. Among 16 compounds, compounds (1), (2), (3), (4), (6), (7), and (9) demonstrated excellent urease inhibitory activity with IC50 values (9.8 ± 0.5, 11.0 ± 0.6, 16.0 ± 1.5, 17.2 ± 0.5, 15.4 ± 0.5, 19.7 ± 0.4, and 15.8 ± 0.2μM), respectively, even better than the standard thiourea (IC50 = 21 ± 0.01μM). However, compound (8) shows an almost same level of inhibition (IC50 = 22.9 ± 0.3μM), as like standard. In this work, we reported for the first time urease inhibitory activity of thiadiazine thiones and its molecular docking studies. [ABSTRACT FROM AUTHOR]

A series of hydrazones 5a-i were synthesized by the condensation of hydrazides derived from dichlorophenylacetic acids with different aromatic aldehydes and ketones. Their structures were confirmed by spectroscopic data and elemental analysis. Hydrazones 5a-i were evaluated for α-glucosidase and urease inhibition activities. Five compounds exhibited potent α-glucosidase inhibitory potential with IC50 values 8.5 ± 0.3, 22.2 ± 0.78, 32.9 ± 1.5, 34 ± 2.4, and 170.6 ± 7.5 μM, respectively, which are many times better than that of the standard inhibitor acarbose ( IC50 = 840 ± 1.73 μM). Furthermore, molecular docking study was performed to explore the binding mode in the active sites of α-glucosidase and urease enzymes. [ABSTRACT FROM AUTHOR]

In addition to catalytic action, snake venom phospholipase A2 induces several pharmacological effects including neurotoxicity, cardiotoxicity as well as anti-coagulant and anti-platelet aggregation effects. Therefore, strategy to identify dual inhibitor for this enzyme will be of much importance in medical research. In this paper, structure-based pharmacophore mapping, molecular docking, protein-ligand interaction fingerprints, binding energy calculations, and binding affinity predictions were employed in a virtual screening strategy to identify new hits for dual inhibition of anti-coagulation and inflammation of phospholipase A2. A structure-based pharmacophore map was modeled which comprised of important interactions as observed in co-crystal of phospholipase A2 and its dual inhibitor indomethacin. The generated model was used to retrieve molecules from ChemBridge, a free database of commercially available compounds. A total of 381 molecules mapped on the developed pharmacophore model from ChemBridge database. The hits retrieved were further screened by molecular docking, protein-ligand interaction fingerprints, binding energy calculations, and binding affinity predictions using Genetic Optimization for Ligand Docking and moe. Based on these results, 32 chemo-types molecules were predicted as potential lead scaffolds for developing novel, potent and structurally diverse dual inhibitor of phospholipase A2. [ABSTRACT FROM AUTHOR]

In addition to catalytic action, snake venom phospholipase A2 induces several pharmacological effects including neurotoxicity, cardiotoxicity as well as anti-coagulant and anti-platelet aggregation effects. Therefore, strategy to identify dual inhibitor for this enzyme will be of much importance in medical research. In this paper, structure-based pharmacophore mapping, molecular docking, protein-ligand interaction fingerprints, binding energy calculations, and binding affinity predictions were employed in a virtual screening strategy to identify new hits for dual inhibition of anti-coagulation and inflammation of phospholipase A2. A structure-based pharmacophore map was modeled which comprised of important interactions as observed in co-crystal of phospholipase A2 and its dual inhibitor indomethacin. The generated model was used to retrieve molecules from ChemBridge, a free database of commercially available compounds. A total of 381 molecules mapped on the developed pharmacophore model from ChemBridge database. The hits retrieved were further screened by molecular docking, protein-ligand interaction fingerprints, binding energy calculations, and binding affinity predictions using Genetic Optimization for Ligand Docking and moe. Based on these results, 32 chemo-types molecules were predicted as potential lead scaffolds for developing novel, potent and structurally diverse dual inhibitor of phospholipase A2. [ABSTRACT FROM AUTHOR]

In addition to catalytic action, snake venom phospholipase A(2) induces several pharmacological effects including neurotoxicity, cardiotoxicity as well as anti-coagulant and anti-platelet aggregation effects. Therefore, strategy to identify dual inhibitor for this enzyme will be of much importance in medical research. In this paper, structure-based pharmacophore mapping, molecular docking, protein-ligand interaction fingerprints, binding energy calculations, and binding affinity predictions were employed in a virtual screening strategy to identify new hits for dual inhibition of anti-coagulation and inflammation of phospholipase A(2) . A structure-based pharmacophore map was modeled which comprised of important interactions as observed in co-crystal of phospholipase A(2) and its dual inhibitor indomethacin. The generated model was used to retrieve molecules from ChemBridge, a free database of commercially available compounds. A total of 381 molecules mapped on the developed pharmacophore model from ChemBridge database. The hits retrieved were further screened by molecular docking, protein-ligand interaction fingerprints, binding energy calculations, and binding affinity predictions using Genetic Optimization for Ligand Docking and moe. Based on these results, 32 chemo-types molecules were predicted as potential lead scaffolds for developing novel, potent and structurally diverse dual inhibitor of phospholipase A(2.)., (© 2011 John Wiley & Sons A/S.)