Arylpyrazole as selective anti-enterococci; synthesis and biological evaluation of novel derivatives for their antimicrobial efficacy

Exploring the structure–activity relationships (SAR) of a new set of phenylpyrazoles unveiled a potential anti-enterococcus lead compound 12 . The benzofuran moiety linked to the phenylpyrazole 12 was 32 times better than vancomycin against Enterococcus faecalis ATCC 51299. Besides, compound 12 is expected to have an excellent oral bioavailability according to the in silico studies. Of SAR analysis, we found that the benzofuran side chain was essential for the activity. Changing the benzofuran with either benzothiophene, phenyl, pyridinyl, tolyl, or naphthyl reduces/nullifies the pharmacological action. Besides the anti-enterococcal activity, derivatives 4 and 6 can be used to develop new broad-spectrum antibiotics as they exhibited activity against the wild-type highly virulent Escherichia coli isolate. Moreover, compound 13 was proved to show antifungal activity (MIC = 4 μg/ml) against the Candida albicans SS5314 (wild type). Finally, the in silico analysis showed that those compounds have good profiles regarding the absorption, distribution, metabolism, and excretion studies, drug-likeness and pharmacokinetics properties.     

Copper(II) complexation with 1-methyl-2-mercaptoimidazole in 7 M HCl

The complexation of copper(II) with 1-methyl-2-mercaptoimidazole in 7 M HCl was potentiometrically studied. The compositions of complexes were determined, and their stepwise formation constants were calculated. The complexes were shown to become less stable with increasing temperature. The thermodynamic functions of complexation were estimated. The copper complexes were shown to surpass the rhenium complexes in stability.     

Synthesis and mass cytometric analysis of lanthanide-encoded polyelectrolyte microgels

This article describes the synthesis and characterization of two series of functional polyelectrolyte copolymer microgels intended for bioassays based upon mass cytometry, a technique that detects metals by inductively coupled plasma mass spectrometry (ICP-MS). The microgels were loaded with Eu(III) ions, which were then converted in situ to EuF(3) nanoparticles (NPs). Both types of microgels are based upon copolymers of N-isopropylacrylamide (NIPAm) and methacrylic acid (MAA), poly(NIPAm/VCL/MAA) (VCL = N-vinylcaprolactam, V series), and poly(NIPAm/MAA/PEGMA) (PEGMA = poly(ethylene glycol)methacrylate, PG series). Very specific conditions (full neutralization of the MAA groups) were required to confine the EuF(3) NPs to the core of the microgels. We used mass cytometry to measure the number and the particle-to-particle variation of Eu ions per microgel. By controlling the amount of EuCl(3) added to the neutralized microgels. we could vary the atomic content of individual microgels from ca. 10(6) to 10(7) Eu atoms, either in the form of Eu(3+) ions or EuF(3) NPs. Leaching profiles of Eu ions from the hybrid microgels were measured by traditional ICP-MS.     

Optical and structural characterization of ultrananocrystalline diamond/hydrogenated amorphous carbon composite films deposited via coaxial arc plasma

Ultrananocrystalline diamond/hydrogenated amorphous carbon composite films were deposited in the ambient of hydrogen by coaxial arc plasma deposition. The film compositions and chemical bonding structures were investigated by X-ray diffraction, X-ray photoemission and hydrogen forward scattering spectroscopies. The sp³/(sp²+sp³) ratio and hydrogen content in the film were estimated to be 64% and 35?at.%, respectively. The optical parameters and the optical dispersion profile were determined by using a variable angle spectroscopic ellipsometer at 55°, 65° and 75° angle of incidence in the photon energy range of 0.9–5?eV. Combinations of multiple Gaussian, and Tauc-Lorentz or Cody-Lorentz dispersion functions are used to reproduce the experimental data. Results of ellipsometry showed a refractive index of approximately 2.05 (at 2eV) and optical band gap of 1.63?eV. The imaginary part of dielectric function exhibited a peak at 3.8?eV, which has assigned to π-π* electron transitions. Furthermore, Electron spin resonance measurements implied the existence of dangling bonds, which might have a partial contribution to the optical absorption properties of the deposited films. A correlation between optical parameters and structural profile of the deposited films is discussed.     

Solvent-Free Synthesis,In Vitro and In Silico Studies of Novel Potential 1,3,4-Thiadiazole-Based Molecules against Microbial Pathogens

A new series of 1,3,4-thiadiazoles was synthesized by the reaction of methyl 2-(4-hydroxy-3-methoxybenzylidene) hydrazine-1-carbodithioate (2) with selected derivatives of hydrazonoyl halide by grinding method at room temperature. The chemical structures of the newly synthesized derivatives were resolved from correct spectral and microanalytical data. Moreover, all synthesized compounds were screened for their antimicrobial activities using Escherichia coli, Pseudomonas aeruginosa, Proteus vulgaris, Bacillus subtilis, Staphylococcus aureus, and Candida albicans. However, compounds 3 and 5 showed significant antimicrobial activity against all tested microorganisms. The other prepared compounds exhibited either only antimicrobial activity against Gram-positive bacteria like compounds 4 and 6, or only antifungal activity like compound 7. A molecular docking study of the compounds was performed against two important microbial enzymes: tyrosyl-tRNA synthetase (TyrRS) and N-myristoyl transferase (Nmt). The tested compounds showed variety in binding poses and interactions. However, compound 3 showed the best interactions in terms of number of hydrogen bonds, and the lowest affinity binding energy (−8.4 and −9.1 kcal/mol, respectively). From the in vitro and in silico studies, compound 3 is a good candidate for the next steps of the drug development process as an antimicrobial drug.     

Electrokinetic Size and Mobility Traps for On‐site Therapeutic Drug Monitoring

The extraction of target analytes from biological samples is a bottleneck in analysis. A microfluidic device featuring an electrokinetic size and mobility trap was formed by two nanojunctions of different pore size to extract and concentrate analytical targets from complex samples. The trap was seamlessly coupled with electrophoretic separation for quantitative analysis. The device was applied to the analysis of ampicillin levels in blood within 5 min and a linear response over the range of 2.5–20 μg mL^?1. This covers the recommended levels for treating sepsis, a critical condition with 30 to 50 % mortality and unpredicted drug levels. The device provides a new opportunity for on‐site therapeutic drug monitoring, which should enable quick and accurate dosing and may save lives in such critical conditions.     

Microbial Transformation of Isolongifolen‐4‐one

The microbial transformation of (+)‐isolongifolen‐4‐one ( 4 ) by a number of fungi by means of a standard two‐stage fermentation technique afforded (7R)‐12‐hydroxyisolongifolen‐4‐one ( 5 ), (7S)‐13‐hydroxyisolongifolen‐4‐one ( 6 ), (11R)‐11‐hydroxyisolongifolen‐4‐one ( 7 ), (10R)‐10‐hydroxyisolongifolen‐4‐one ( 8 ), and (9R)‐9‐hydroxyisolongifolen‐4‐one ( 9 ) (Scheme). All five metabolites were found to be new, and metabolites 6 and 9 showed potent tyrosinase inhibitory activity (Table 1). The metabolites and their derivatives were characterized on the basis of spectroscopic and single‐crystal X‐ray‐diffraction techniques.     

Bivariate Sarmanov Phase-Type Distributions for Joint Lifetimes Modeling

Methodology and Computing in Applied Probability - In this paper, we are interested in the dependence between lifetimes based on a joint survival model. This model is built using the bivariate...     

Effect of variation of the structure of amino acids on inhibition of the corrosion of low-alloy steel in ammoniated citric acid solutions

Potentiodynamic polarization, electrochemical impedance spectroscopy, and the new technique electrochemical frequency modulation were used to study the effect of the different structures of three amino acids (tryptophan, tyrosine, and serine) on inhibition of the corrosion of ASTM A213 grade T22 low-alloy steel in ammoniated citric acid solutions. The effects on corrosion inhibition of inhibitor concentration, temperature, and stirring velocity were studied. Thermodynamic data for corrosion and adsorption were calculated and are discussed. The results obtained from the different techniques reveal that the efficiency of inhibition follows the sequence: tryptophan > tyrosine > serine. Inhibition occurs as a result of adsorption of inhibitor molecules by the alloy surface. Adsorption of the inhibitors is a good fit with the Temkin isotherm model.