Enhancement of Antibiotic Activity by 1,8-Naphthyridine Derivatives against Multi-Resistant Bacterial Strains

The search for new antibacterial agents has become urgent due to the exponential growth of bacterial resistance to antibiotics. Nitrogen-containing heterocycles such as 1,8-naphthyridine derivatives have been shown to have excellent antimicrobial properties. Therefore, the purpose of this study was to evaluate the antibacterial and antibiotic-modulating activities of 1,8-naphthyridine derivatives against multi-resistant bacterial strains. The broth microdilution method was used to determine the minimum inhibitory concentration (MIC) of the following compounds: 7-acetamido-1,8-naphthyridin-4(1H)-one and 3-trifluoromethyl-N-(5-chloro-1,8-naphthyridin-2-yl)-benzenesulfonamide. The antibiotic-modulating activity was analyzed using subinhibitory concentrations (MIC/8) of these compounds in combination with norfloxacin, ofloxacin, and lomefloxacin. Multi-resistant strains of Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus were used in both tests. Although the compounds had no direct antibacterial activity (MIC ≥ 1.024 µg/mL), they could decrease the MIC of these fluoroquinolones, indicating synergism was obtained from the association of the compounds. These results suggest the existence of a structure–activity relationship in this group of compounds with regard to the modulation of antibiotic activity. Therefore, we conclude that 1,8-naphthyridine derivatives potentiate the activity of fluoroquinolone antibiotics against multi-resistant bacterial strains, and thereby interesting candidates for the development of drugs against bacterial infections caused by multidrug resistant strains.     

Alkenyl Boronates: Synthesis and Applications

Organoboron compounds have become one of the most versatile building blocks in organic synthesis owing to their accessible and efficient conversion into many different functional groups. In particular, alkenyl boronates have received a great deal of attention as very reactive substrates in Suzuki–Miyaura cross‐coupling reactions. Accordingly, efforts towards the development of efficient methods to prepare this type of compound are ongoing. In this contribution, the progress in the search for synthetic routes for alkenyl boronates and their use in a variety of organic transformations is accounted.     

Method for Finding the Exact Effective Hamiltonian of Time‐Driven Quantum Systems

Time‐driven quantum systems are important in many different fields of physics as cold atoms, solid state, optics, etc. Many of their properties are encoded in the time evolution operator or the effective Hamiltonian. Finding these operators usually requires very complex calculations that often involve some approximations. To perform this task, a systematic scheme that can be cast in the form of a symbolic computational algorithm is presented. It is suitable for periodic and non‐periodic potentials and, for convoluted systems, can also be adapted to yield numerical solutions. The method exploits the structure of the associated Lie group and a decomposition of the evolution operator on each group generator. To illustrate the use of the method, five examples are provided: harmonic oscillator with time‐dependent frequency (Paul trap), modulated optical lattice, time‐driven quantum oscillator, a step‐wise driving of a free particle, and the non‐periodic Caldirola‐Kanai Hamiltonian. To the extent of the authors' knowledge, whereas the exact form of Paul trap's evolution operator is well known, its effective Hamiltonian was until now unknown. The remaining four examples accurately reproduce previous results.     

Selection of ethylene-vinyl-acetate properties for modified bitumen with enhanced end-performance

Bitumen modification with ethylene-vinyl acetate (EVA), in a wide range temperatures (between ??30 and 100 °C), has been studied as a function of polymer concentration and EVA characteristics (vinyl acetate (VA) content and melt flow index (MFI)). Viscous flow, dynamic shear (DSR) temperature sweep, and technological tests were conducted to assess binder performance at medium-to-high in-service temperatures. Evaluation of binder low-temperature viscoelastic behavior has been performed using a solid rectangular fixture (SRF) in torsional mode, either in the linear viscoelastic region or under non-linear conditions (by strain breakage tests between ??30 and 0 °C). Further microstructural analysis based on modulated differential scanning calorimetry (MDSC) and optical microscopy was conducted to support rheological and technological results. Hence, total crystalline fraction (related to the VA content and polymer concentration) turned out to be a key parameter to achieve a suitable binder modification at medium-high temperatures. In addition, MFI appears to be an important EVA parameter at low temperatures, as it was found that lower MFI values enhanced resistance to low-temperature cracking.     

Algebraic PGD for tensor separation and compression: An algorithmic approach

Proper Generalized Decomposition (PGD) is devised as a computational method to solve high-dimensional boundary value problems (where many dimensions are associated with the space of parameters defining the problem). The PGD philosophy consists in providing a separated representation of the multidimensional solution using a greedy approach combined with an alternated directions scheme to obtain the successive rank-one terms. This paper presents an algorithmic approach to high-dimensional tensor separation based on solving the Least Squares approximation in a separable format of multidimensional tensor using PGD. This strategy is usually embedded in a standard PGD code in order to compress the solution (reduce the number of terms and optimize the available storage capacity), but it stands also as an alternative and highly competitive method for tensor separation.     

Influence of pre-shearing on rheometric measurements of an oil-based drilling fluid

Drilling fluids are suspensions of solid particles and present thixotropic and elastoviscoplastic behaviors simultaneously, which turn their rheological characterization into a challenging task. Rotational rheometers are widely employed to determine the properties of these fluids, and one major challenge in rheometric tests carried out with thixotropic fluids is to obtain repeatable results. Submitting the fluid specimen to a known shear history by performing a pre-shear procedure is commonly used to achieve repeatable results with thixotropic fluids. In this paper, the effect of different pre-shearing conditions on the rheological measurements of an oil-based drilling fluid was investigated using cross-hatched parallel plates. Firstly, an adequate aging time to ensure complete fluid restructuring was determined by monitoring the storage modulus, G′, over an oscillatory time sweep experiment. Shear-rate controlled start-up tests were then conducted to evaluate the gel strength and the steady-state shear stress. Nine different pre-shearing conditions were evaluated, and each experiment was performed three times. Finally, the results were analyzed by using two statistical tools: a two-way analysis of variance (ANOVA) and the Tukey’s range test. The analysis shows that despite the good repeatability achieved when the same pre-shear condition is applied, the pre-shearing affects not only the gel strength but also the steady-state shear stress. The ANOVA also revealed that the effect of the pre-shearing shear rate on the fluid rheological behavior is statistically more significant than the effect of the pre-shearing time. The same analysis was performed after 10 s and 10 min of aging, and similar results were obtained.     

Design and Synthesis In Silico Drug-like Prediction and Pharmacological Evaluation of Cyclopolymethylenic Homologous of LASSBio-1514

Acylhydrazones are still an important framework to the design of new bioactive compounds. As treatment of chronic pain represents a clinical challenge, we decided to modify the structure of LASSBio-1514 (1), previously described as anti-inflammatory and analgesic prototype. Applying the homologation as a strategy for molecular modification, we designed a series of cyclopentyl- (2a–e), cyclobutyl- (3a–e), and cyclopropylacylhydrazones (4a–e) that were synthetized and evaluated in murine models of inflammation and pain. A comparison of their in silico physicochemical and drug-like profile was conducted, as well as their anti-inflammatory and analgesic effect. Compounds 4a (LASSBio-1755) and 4e (LASSBio-1757) displayed excellent in silico drug-like profiles and were identified as new analgesic lead-candidates in acute and chronic model of pain, through oral administration.     

Structure of liquid-vapor interface of square well fluid confined in a cylindrical pore

By means of the canonical Monte Carlo simulations, the vapor-liquid (VL) equilibrium and structure of square well (SW) fluids confined in a single cylindrical pore with repulsive surface, have been studied. Coexistence curves of the confined VL interface are determined for a wide range of temperatures and pore diameters. It is demonstrated that the confinement not only reduces the VL coexistence region but also induces strong inhomogeneities of the VL interface: coexistence liquid densities are different at the pore center and at the wall surface. It may be considered as a preliminary step for an isolated droplet formation inside the pore, as well as a tentative reason of the two VL phase transitions of simple fluids adsorbed into disordered porous media.