Cationic polyrotaxanes effectively inhibit uptake via carnitine/organic cationic transporters without cytotoxicity

We examined the inhibitory effect of cationic polyrotaxanes, which consist of alpha-cyclodextrins threaded on a poly(ethylene glycol) (PEG) chain, on the activity of the intestinal carnitine/organic cation transporter, OCTN2, in OCTN2 gene-transfected HEK293/PDZK1 cells. The cationic polyrotaxanes effectively inhibited the OCTN2-mediated carnitine transport. Polyrotaxanes with a longer PEG chain exhibited a greater inhibitory effect, possibly owing to multivalent interactions with binding sites on OCTN2. These cationic polyrotaxanes were far less cytotoxic than conventional polycations, and are therefore interesting candidates as low-toxicity inhibitors of cation transport at cell surfaces.     

Annulated bicyclic isothioureas: identification of active and selective butyrylcholinesterase inhibitors

Structural optimization of butyrylcholinesterase inhibitors, 5-bromomethyl- and 5-iodomethyl-N,N-disubstituted 2-aminothiazolines, led to a series of their annulated bicyclic analogues, obtained by intramolecular cyclization of cycloalkenylthioureas. The most active compound in this series, cyclohepta[d]thiazol-2-amine, is a mixed-type butyryl-cholinesterase inhibitor with IC₅₀ = 130 nm, highly selective compared to acetylcholinesterase and non-toxic at 100 μm concentrations.     

Use of fluorinated functionality in enzyme inhibitor development: Mechanistic and analytical advantages

On the one hand, owing to its electronegativity, relatively small size, and notable leaving group ability from anionic intermediates, fluorine offers unique opportunities for mechanism-based enzyme inhibitor design. On the other, the “bio-orthogonal” and NMR-active 19-fluorine nucleus allows the bioorganic chemist to follow the mechanistic fate of fluorinated substrate analogues or inhibitors as they are enzymatically processed. This article takes an overview of the field, highlighting key developments along these lines. It begins by highlighting new screening methodologies for drug discovery that involve appropriate tagging of either the substrate or an array of potential substrates (i.e. in proteomics screens) with ¹⁹F-markers that then report back on turnover and function, respectively, via the NMR screen. Taking this one step further, substrate-tagging with fluorine can be done in such a manner as to provide stereochemical information on enzyme mechanism. For example, substitution of one of the terminal hydrogens in phosphoenolpyruvate, provides insight into the, otherwise latent, facial selectivity of CC bond formation in KDO synthase. Perhaps, most importantly, from the point of view of this discussion, appropriately tailored fluorinated functionality can be used to form stabilized “transition state analogue” complexes with target enzymes. Thus, 5-fluorinated pyrimidines, α-fluorinated ketones, and 2-fluoro-2-deoxysugars each lead to covalent adduction of catalytic active site residues in thymidylate synthase (TS), serine protease and glycosidase enzymes, respectively. In all such cases, ¹⁹F NMR allows the bioorganic chemist to spectrally follow “transition state analogue” formation. Finally, the use of specific fluorinated functionality to engineer “suicide substrates” is highlighted in a discussion of the development of the α-(2′Z-fluoro)vinyl trigger for amino acid decarboxylase inactivation. Here ¹⁹F NMR allows the bioorganic chemist to glean useful partition ratio data directly from the NMR tube.     

Interfacial reactions between Al7075 alloy and BaAl2Si2O8 + CaAl2Si2O8 mixture

The present work reports the SEM, EPMA and TEM examination of reactions at the interface of Al7075 alloy and a 50/50 wt% mixture of BaAl₂Si₂O₈ + CaAl₂Si₂O₈ feldspars at 850 °C, 1150 °C and 1250 °C. Sintering of the feldspar mixture at 1450 °C caused dissolution of ~1.0 wt% Ca in BaAl₂Si₂O₈ and 0.5 wt% Ba in CaAl₂Si₂O₈. The interaction of the Al alloy with the sintered feldspars shifted the alloy composition to the Al–Si–αBaAl₂Si₂ and Al–Si–βaAl₂Si₂ compatibility triangles. The feldspars underwent a series of phase transformations, leading ultimately to the formation of Al₂O₃.     

A simpler sampling interface of venturi easy ambient sonic-spray ionization mass spectrometry for high-throughput screening enzyme inhibitors

High-throughput screening (HTS) is often required in enzyme inhibitor drugs screening. Mass spectrometry (MS) provides a powerful method for high-throughput screening enzyme inhibitors because its high speed, sensitivity and property of lable free. However, most of the MS methods need complicated sampling interface system. Overall throughput was limited by sample loading in these cases. In this study, we develop a simple interface which coupled droplet segmented system to a venturi easy ambient sonic-spray ionization mass spectrometer. It is fabricated by using a single capillary to act as both sampling probe and the emitter, which simplifies the construction, reduces the cost and shorten the sampling time. Samples sucked by venturi effect are segmented to nanoliter plugs by air, then the plugs can be detected by MS directly. This system eliminated the need for flow injection which was popular used in classic scheme. The new system is applied to screen angiotensin converting enzyme inhibitors. High-throughput was achieved in analyzing 96 samples at 1.6 s per sample. The plugs formation was at 0.5s per sample. Carry-over between samples was less than 5%, the peak height RSD was 2.92% (n = 15). Dose-response curves of 3 known inhibitors were also measured to validate its potential in drug discovery. The calculated IC₅₀ agreed well with reported values.     

Novel use of glow discharge optical emission spectroscopy (GDOES) to study corrosion of AA2024‐T3 in the presence and absence of inhibitors – part 3: investigating the effects of various proportions of inhibitor in the coating matrix or in nanocontainers

Elemental depth profiling by glow discharge optical emission spectroscopy has been used to characterize the corrosion products on AA2024‐T3. In previous work, the aluminium, oxygen and copper depth profiles were shown to provide information regarding surface roughening, the thickness of corroded layers and extent of copper de‐alloying/relocation. Nitrogen, sulfur, phosphorus and chromium depth profiles were examined in the hope of detecting inhibitor species within the corroded/altered layers after 5 h of exposure to a corrosive solution. In the present work, the study is extended to longer exposure time. The work presents a further study of the leaching of benzotriazole from the coating matrix or from nanocontainers during various times of exposure to a corrosive environment. Copyright © 2016 John Wiley & Sons, Ltd.     

High‐performance liquid chromatography with diode array detection method for the simultaneous determination of seven selected phosphodiesterase‐5 inhibitors and serotonin reuptake inhibitors used as male sexual enhancers

This work presents a simple, sensitive and generic high‐performance liquid chromatography with diode array detection method for the simultaneous determination of seven drugs prescribed for the treatment of erectile dysfunction and premature ejaculation. Investigated drugs include the phosphodiesterase‐5 inhibitors: sildenafil, tadalafil, and vardenafil, in addition to the selective serotonin reuptake inhibitors: dapoxetine, duloxetine, fluoxetine, and paroxetine. The drugs were separated using a Waters C8 column (4.6 × 250 mm, 5 μm) with the mobile phase consisting of phosphate buffer pH 3, acetonitrile and methanol in the ratio 60:33:7. The flow rate was 1.2 mL/min, and quantification was based on measuring peak areas at 225 nm. Peaks were perfectly resolved with retention times 3.3, 3.9, 6.4, 7.5, 9.5, 10.7, and 13.4 min for vardenafil, sildenafil, paroxetine, duloxetine, dapoxetine, fluoxetine, and tadalafil, respectively. The developed method was validated with respect to system suitability, linearity, ranges, accuracy, precision, robustness, and limits of detection and quantification. The proposed method showed good linearity in the ranges 5–500, 2–200, 2–200, 3–300, 1.5–150, 2–200, and 2–200 μg/mL for sildenafil, tadalafil, vardenafil, dapoxetine, duloxetine fluoxetine, and paroxetine, respectively. The limits of detection were 0.18–0.38 μg/mL for the analyzed compounds. The applicability of the proposed method to real life situations was assessed through the analysis of commercial tablets, and satisfactory results were obtained.     

The Effect of Magnetic Field on Corrosion Inhibitor of Copper in 0.5 M HCl Solution

Corrosion of metals within magnetic field (MF) had been actively studied for better understanding of the corrosion mechanism when the magnetic sources are presented. However, findings regarding the effect of MF on metals are inconclusive, and there is a lack of studies of MF interaction with various corrosion control techniques, such as corrosion inhibitor. In this paper, the effect of MF on the corrosion of copper in 0.5 M hydrochloric acid (HCl) solution, with or without corrosion inhibitor were studied. Benzotriazole (BTA), a common copper inhibitor, was chosen as the inhibitor for this study. To determine the effect of MF, a MF of 13 mT, generated using a pair of permanent neodymium magnet, was applied during weight loss and electrochemical tests. The results showed that corrosion inhibition efficiency of BTA decreased when it is under an applied MF. A decrease from 47% to 60% in inhibition efficiency had been observed for all samples in an applied MF. By using Tafel extrapolation technique on the polarization curves, it revealed that MF had increased the corrosion current of copper in HCl, causing a decrease in the inhibition efficiency.     

Green approach to corrosion inhibition of mild steel in hydrochloric acid medium using extract of spirogyra algae

In the present investigation, a fresh water green algae spirogyra is used as an inexpensive and efficient mild steel corrosion inhibitor. The study is carried out in 0.5?M HCl solution using weight loss measurements, scanning electron microscopy–energy-dispersive X-ray spectroscopy, X-ray diffraction, and Fourier transforms infrared (FT-IR) techniques. The maximum inhibition efficiency was found to be 93.03% at 2?g?L^?1. The adsorption of extract of spirogyra on mild steel surface obeys the Langmuir adsorption isotherm. Corrosion inhibition mechanisms were inferred from the temperature dependence of the inhibition efficiency as well as from calculation of thermodynamic and kinetic parameters which direct the process. FT-IR analysis of green algae spirogyra revealed the presence of hydroxyl, amino, and carbonyl groups, which are responsible for the adsorption on the mild steel surface. SEM analysis supported the inhibitive action of the spirogyra extract against the mild steel corrosion in acid solution.