The nonlinear boundary value problem for a class of integro-differential system

In this paper, using the theory of differential inequalities, we study the nonlinear boundary value problem for a class of integro-differential system. Under appropriate assumptions, the existence of solution is proved and the uniformly valid asymptotic expansions for arbitrary n-th order approximation and the estimation of remainder term are obtained simply and conveniently.     

Determination of ticagrelol in rat plasma and tablets by micellar electrokinetic chromatography coupled with large volume sample stacking: Application to a pharmacokinetic study

A method using micellar electrokinetic chromatography coupled with large-volume sample stacking for the determination of ticagrelol was developed and validated. The analysis was performed in a fused silica capillary (41.5 cm effective length, 50 μm diameter) with ultraviolet detection at 195 nm. The background electrolytes were 30 mM phosphate buffer of pH 3.0 with 120 mM sodium dodecylsulfate and 10 % (v/v) acetonitrile (120 s X 50 mbar; 20°C; -18 kV) and 30 mM borate buffer of pH 8.5 with 75 mM sodium dodecylsulfate (120 s X 50 mbar; 20°C; 25 kV); under acidic and alkaline conditions, respectively. The method was found to be reliable with respect to specificity, linearity of the calibration line (R² > 0.99), repeatability (relative standard deviation 2.56%–3.34%), and accuracy (recovery in the range 101.21%–102.67%). The limits of detection and quantitation were 0.032, 0.071, and 0.087, 0.188 μg/mL, respectively. The method was successfully applied for the determination of ticagrelol concentrations in rat plasma and tablets with good recoveries and reproducibility. The presented method proved to be suitable for monitoring ticagrelor in rat plasma.     

Exploring the interaction between 3-D structure of TLR 9 and prostaglandin analogues

Toll-like receptor 9 (TLR9) is a class of pattern recognition receptors (PRRs) approved to have an essential role with the development of autoimmune illnesses such as psoriasis and arthritis. TRL9 is predominantly expressed on dendritic cells (DCs) and macrophages, and it mediates antigen presentation to T cells. In this regard, interfering with this interaction by inhibiting TLR9 could be an effective immunotherapy strategy for certain diseases. Based on previous research (Degraaf et al.2014, Farrugia et al., 2017) indicating that prostaglandins play a significant role in regulating or reducing the expression of TLRs, their function against intracellular TLRs such as TLR9 may involve direct inhibition of these receptors. The 3D structure of the human-TLR9 is modelled and described molecularly and then prepared to be docked by prostaglandin analogues, followed by molecular dynamic (MD) simulation, MM/PBSA analysis, and PCA analysis. The study uncovered significant direct interactions between TLR9 and prostaglandin analogues, specifically with the FDA-approved Bimatoprost (BI), which demonstrates the highest binding affinity (calculated as an estimated affinity) and an interesting MM/PBSA score and should be the primary focus of future research into the treatment of autoimmune diseases. In addition, the modelled structure of human-TLR9 and its binding site described in this study could serve as a useful starting point for the development of additional inhibitors.     

氢气燃烧火焰颜色影响因素的研究及演示方案再设计

基于对氢气燃烧火焰颜色的不同解释,从焰色反应、火焰温度、气体流速等3方面影响因素设计方案进行实验研究,得出影响氢气火焰颜色的主要因素是气流速度、火焰温度及药品的焰色反应。巧用球形干燥管既控制气流速度、又控制火焰温度的特点,设计出可以观察到氢气燃烧火焰呈明显蓝色的演示装置。用可现取的仪器药品、可执行的实验方案、可重现的实验现象、可检验的实验结果,验证了教材中关于氢气燃烧火焰颜色的论述,突破了实际操作中氢气燃烧颜色不易观察的局限。     

Synthesis,spectral characterization,thermal study and antimicrobial activity of (E)-4-(substituted 1-Benzo[d]imidazole-2-yl)-N'-(substituted Benzylidene)benzohydrazide schiff bases

Antimicrobial properties casing wide applicability in water detoxification, pharmaceutics and in industries. Present work focus on the synthesis of a new series of Schiff Bases (E)-4-(1 substituted-1H Benzo[d]imidazole-2-yl)-N'-(substituted Benzylidene)benzohydrazide (5a-5l) were synthesized. The convenient route for the synthesis of new analogues by the condensation of 4-(substituted -1H-Benzo[d]imidazole-2-yl)-N'- Hydrazine with different derivatives of aromatic aldehydes were described using different solvents and catalysts. The structures of the synthesized compounds were ascertain by spectral techniques viz. IR, ¹H NMR, MS and Physical Elemental data. Compounds were also subjected to thermal analysis to study their physical and chemical properties. The title compounds were also screened for their antimicrobial activity against various bacterial & Fungal strains. Results of bioassay vary with diverse group attached to Benzimdazole motif and could be helpful for the development of other bioactive molecules.     

Synthesis,characterization, computational,excited state properties,wave function and molecular docking studies of (E)-1-(perfluorophenyl)-N-(p-tolyl) methanimine

The compound (E)-1-(perfluorophenyl)-N-(p-tolyl)methanimine (PFPT) was synthesized and characterized by the Infrared, UV–Visible, and NMR analysis. Using density functional theory, the current work is a set of theoretical studies on PFPT. The compound molecular structure and geometry were defined using DFT. Topological studies, like electron localized function, localized orbital locator, average localized ionization energy, and reduced density gradient studies, were done with the Multiwfn-3.8 to find the main binding areas and weak interactions in the molecule. Using the IEFPCM solvation model used to study the calculated UV–Visible spectrum, we used two different solvents. The HOMO-LUMO, MEP, and NLO properties were carried out by DFT/B3LYP/cc-pVDZ in the gas phase. The NBO calculations are used to study how charges move between and within the molecule and the stability of this molecule. A pharmacological analysis is done using an online tool like Swiss-ADME, to see if the molecule could be a potential drug candidate; this evaluation looks at the drug-likeness, ADME, and eco-friendly toxicity properties of the PFPT molecule. Auto-dock suite and Discovery studio Visualizer are used to do molecular docking against 2QFA protein.     

Understanding the Influence of Donor-Acceptor Diazo Compounds on the Catalyst Efficiency of B(C6F5)3 Towards Carbene Formation

Diazo compounds have been largely used as carbene precursors for carbene transfer reactions in a variety of functionalization reactions. However, the ease of carbene generation from the corresponding diazo compounds depends upon the electron donating/withdrawing substituents either side of the diazo functionality. These groups strongly impact the ease of N₂ release. Recently, tris(pentafluorophenyl)borane [B(C₆F₅)₃] has been shown to be an alternative transition metal-free catalyst for carbene transfer reactions. Herein, a density functional theory (DFT) study on the generation of carbene species from α-aryl α-diazocarbonyl compounds using catalytic amounts of B(C₆F₅)₃ is reported. The significant finding is that the efficiency of the catalyst depends directly on the nature of the substituents on both the aryl ring and the carbonyl group of the substrate. In some cases, the boron catalyst has negligible effect on the ease of the carbene formation, while in other cases there is a dramatic reduction in the activation energy of the reaction. This direct dependence is not commonly observed in catalysis and this finding opens the way for intelligent design of this and other similar catalytic reactions.     

Discovery of potential Zika virus RNA polymerase inhibitors by docking-based virtual screening

Zika virus (ZIKV) infection has been associated with Guillain-Barre syndrome in adults and microcephaly in infants. The existence of insufficient structural data in most of the protein databases hinders the synthesis of anti-ZIKV pharmaceutics. In this work, we attempted to model the catalytic domain of the ZIKV RNA polymerase (RdRpC) along with a detailed assessment of conserved aspartates in ZIKV RdRpC palm domain as potential drug targets. The conserved and catalytically active aspartate residues present in the predicted RdRpC protein were virtually screened against a ZINC database for inhibitors, and the selected potential drug candidates were further filtered based on their ADMET profiles. One of the pharmacokinetically active compounds (Ligand 6) showed a remarkable docking profile against the strictly conserved aspartate residues of the RdRpC active site. We hypothesize that the Ligand 6 may form a potential drug candidate for RdRpC inhibition in the clinical treatment of ZIKV infection.     

Exploration of interaction zones of β-tubulin colchicine binding domain of helminths and binding mechanism of anthelmintics

Numerous studies postulated the possible modes of anthelmintic activity by targeting alternate or extended regions of colchicine binding domain of helminth β-tubulin. We present three interaction zones (zones vide −1 to −3) in the colchicine binding domain of Haemonchus contortus (a helminth) β-tubulin homology model and developed zone-wise structure-based pharmacophore models coupled with molecular docking technique to unveil the binding hypotheses. The resulted ten structure-based hypotheses were then refined to essential three point pharmacophore features that captured recurring and crucial non-covalent receptor contacts and proposed three characteristics necessary for optimal zone-2 binding: a conserved pair of H bond acceptor (HBA to form H bond with Asn226 residue) and an aliphatic moiety of molecule separated by 3.75 ± 0.44 Å. Further, an aliphatic or a heterocyclic group distant (11.75 ± 1.14 Å) to the conserved aliphatic site formed the third feature component in the zone-2 specific anthelmintic pharmacophore model. Alternatively, an additional HBA can be substituted as a third component to establish H bonding with Asn204. We discern that selective zone-2 anthelmintics can be designed effectively by closely adapting the pharmacophore feature patterns and its geometrical constraints.