Molecular structural investigations of quinoxaline derivatives through 3D-QSAR,molecular docking,ADME prediction and pharmacophore modeling studies for the search of novel antimalarial agent

In the present article, a dataset of 63 quinoxaline derivatives were taken for antimalarial activity and pharmacophore were developed. Atom based method was used to develop a three dimensional quantitative structure activity relationship (3D-QSAR) model. On comparison of all statistical parameters, model AHRRR23 was found to be the most effective and predictive QSAR model as it satisfied all statistical parameters of a good model. The model AHRRR23 showed an adequate R² value for the training set 0.9446, good predictive power with Q² of 0.6409, good F- value, low SD 0.1218 value and outstanding Pearson-R values and low RMSE 0.2779 values of the model. The docking studies also gives very good results with good RMSD values. 3D QSAR, docking and ADME studies exhibits that the developed model could be employed as a potential lead for further study as antimalarial drug.     

Microhardness measurements of poly(methyl methacrylate) and poly(vinylidene fluoride) polyblends

The preparation of polymer blends of poly(methyl methacrylate) and poly(vinylidene fluoride) in different weight percentages is described. Vickers microhardness measurements have been made to study the effects of load and compositional ratio of the two polymers in polyblend. It is observed that poly(vinylidene fluoride) acts as a plasticizer for poly(methyl methacrylate). Evidence of increasing and decreasing strength of polyblends has been obtained for different compositional ratios of the two polymers.     

Design,Synthesis, Biological Evaluation and In Silico Study of Benzyloxybenzaldehyde Derivatives as Selective ALDH1A3 Inhibitors

Aldehyde dehydrogenase 1A3 (ALDH1A3) has recently gained attention from researchers in the cancer field. Several studies have reported ALDH1A3 overexpression in different cancer types, which has been found to correlate with poor treatment recovery. Therefore, finding selective inhibitors against ALDH1A3 could result in new treatment options for cancer treatment. In this study, ALDH1A3-selective candidates were designed based on the physiological substrate resemblance, synthesized and investigated for ALDH1A1, ALDH1A3 and ALDH3A1 selectivity and cytotoxicity using ALDH-positive A549 and ALDH-negative H1299 cells. Two compounds (ABMM-15 and ABMM-16), with a benzyloxybenzaldehyde scaffold, were found to be the most potent and selective inhibitors for ALDH1A3, with IC₅₀ values of 0.23 and 1.29 µM, respectively. The results also show no significant cytotoxicity for ABMM-15 and ABMM-16 on either cell line. However, a few other candidates (ABMM-6, ABMM-24, ABMM-32) showed considerable cytotoxicity on H1299 cells, when compared to A549 cells, with IC₅₀ values of 14.0, 13.7 and 13.0 µM, respectively. The computational study supported the experimental results and suggested a good binding for ABMM-15 and ABMM-16 to the ALDH1A3 isoform. From the obtained results, it can be concluded that benzyloxybenzaldehyde might be considered a promising scaffold for further drug discovery aimed at exploiting ALDH1A3 for therapeutic intervention.     

Preferential Face‐on and Edge‐on Orientation of Thiophene Oligomers by Rational Molecular Design

Precise control over the supramolecular organization of organic semiconducting materials guiding to exclusive face‐on or edge‐on orientation is a challenging task. In the present work, we study the preferential packing of thiophene oligomers induced through rational molecular designing and self‐assembly. The acceptor–donor–acceptor‐type oligomers having 2‐(1,1‐dicyano‐methylene)rhodanine as acceptor ( OT1 ) favored a face‐on packing, whereas that of functionalized with N‐octyl rhodanine ( OT2 ) preferred an edge‐on packing as evident from 2D‐grazing incidence angle X‐ray diffraction, tapping‐mode atomic force microscopy (AFM) and Raman spectroscopy analyses. The oligomers exhibited anisotropic conductivity in the self‐assembled state as an outcome of the preferred orientation, revealed by the conducting AFM experiment.     

Discovery of Monoacylglycerol Lipase (MAGL) Inhibitors Based on a Pharmacophore-Guided Virtual Screening Study

Monoacylglycerol lipase (MAGL) is an important enzyme of the endocannabinoid system that catalyzes the degradation of the major endocannabinoid 2-arachidonoylglycerol (2-AG). MAGL is associated with pathological conditions such as pain, inflammation and neurodegenerative diseases like Parkinson’s and Alzheimer’s disease. Furthermore, elevated levels of MAGL have been found in aggressive breast, ovarian and melanoma cancer cells. Due to its different potential therapeutic implications, MAGL is considered as a promising target for drug design and the discovery of novel small-molecule MAGL inhibitors is of great interest in the medicinal chemistry field. In this context, we developed a pharmacophore-based virtual screening protocol combined with molecular docking and molecular dynamics simulations, which showed a final hit rate of 50% validating the reliability of the in silico workflow and led to the identification of two promising and structurally different reversible MAGL inhibitors, VS1 and VS2. These ligands represent a valuable starting point for structure-based hit-optimization studies aimed at identifying new potent MAGL inhibitors.     

Radiation induced effects on the microhardness measurements of poly(methyl methacrylate): poly (vinylidene fluoride) polyblends

Solution-mixed poly(methyl methacrylate) (PMMA): poly(vinylidene fluoride) (PVDF) polyblends with different weight percentage ratios were irradiated with various doses of gamma irradiation (1–100 Mrad). The effect of irradiation on the strength of blend specimens was studied by measuring the surface microhardness using a Vickers microhardness tester attached to a Carl Zeiss NU-2 Universal research microscope. The irradiation was found to produce hardening in the blend specimens; however, the degree of hardening depends upon the dose level, testing conditions and also on the miscibility of PMMA and PVDF in the blend specimens. The increase and decrease in microhardness has been explained on the basis of crosslinking and scissioning. The two limits of irradiation dose were 1 and 75 Mrad where significant changes in mechanical strength were observed.     

Zeta potential of colloidal particle in solvent primitive model electrolyte solution: a density functional theory study

A systematic study of zeta potential for a spherical double layer (SDL) around a colloidal particle in electrolyte solutions, is performed using density functional theory and Monte Carlo simulation. The usual recipe under the solvent primitive model is employed to model the system, where macroion, counterions, and coions are represented by charged hard spheres of uniform charge density and the presence of solvent is taken into account by modelling it as neutral hard spheres. All the components of the system are embedded in a dielectric continuum in order to consider the electrostatic effect of the solvent. The density functional theory employs a suitable weighted density approximation to calculate the hard-sphere contribution, whereas the residual electrostatic interactions are calculated as a small perturbation around the uniform fluid. The zeta potential profiles of a SDL in the presence of a number of electrolytes have been calculated and are found to be considerably influenced in the presence of solvent with an increase in the concentration of the electrolyte. The theory successfully predicts the maxima and sign reversal of the zeta potential profiles at high macroion surface charge density and in the presence of multivalent counterions, as obtained from the Monte Carlo simulation.     

Preparation and characterization of Pr2NiO4+δ infiltrated into Gd-doped ceria as SOFC cathode

Journal of Solid State Electrochemistry - Composite electrodes of Pr2NiO4+δ and Gd-doped ceria (Ce0.8Gd0.2O1.90 so-called GDC) have been prepared starting from a Pr-Ni nitrate solution (2:1...     

Ultrasonic Velocities,Densities, and Refractive Indices of Binary Mixtures of Polyethylene Glycol 250 Dimethyl Ether with 1-Propanol and with 1-Butanol

Measurements of the ultrasonic velocity (u), density (ρ) and refractive index (n) for binary mixtures of polyethylene glycol 250 dimethyl ether with 1-propanol and 1-butanol have been made at three temperatures (T=293, 303 and 31 K) over the entire composition range in order to investigate the nature of intermolecular interactions between the components of these liquid mixtures. Various excess thermodynamic properties such as the excess ultrasonic velocity (Δu), deviation in isentropic compressibility (Δk _S ), excess intermolecular free length (L_f^E)(L_{\mathrm{f}}^{\mathrm{E}}), excess acoustic impedance (Z ^E), excess pseudo-Grüneisen parameter (Γ ^E), and molar refraction deviation (ΔR _m) were calculated using experimental values of the ultrasonic velocity, density and refractive index and were then represented with the Redlich-Kister polynomial equation. The observed excess deviation parameter values were explained on the basis of the strength of intermolecular interactions between the components of the mixtures. Estimations of the refractive index and ultrasonic velocity have also been made using various empirical relations and are discussed in terms of the average percentage deviations (APD).     

Ultrasonic and infrared study of molecular interactions in ternary mixtures of 1-naphthol and 2-naphthol with 2-propanone in benzene

The measurements of ultrasonic velocity and density were made for the ternary mixtures of l-naphthol/2-naphthol with 2-propanone in benzene at 20, 30 and 40°C in the mole fraction range of 0.00 to 0.05. Adiabatic compressibility and intermolecular free length have been evaluated using ultrasonic velocity data. The non-linear variation of ultrasonic velocity and allied parameters with mole fraction indicates solute-solute interactions through hydrogen bonding between unlike molecules. Results of ultrasonic velocity and density measurements are further supported by FT-IR spectra. The change in transmittance as well as the shift in the frequency of the representative peak of the OH stretching in FT-IR spectra give inferences about the complex formation.