The superoxide O2·− scavenging reaction of (+)-catechin (Cat), quercetin (Que), rutin, and α-tocopherol (α-TOH) as natural phenolic compounds is investigated on the basis of electrochemical and ESR ...spectral measurements with the aid of density functional theory (DFT) calculations. Reversibility of the O2/O2·− redox couple is significantly affected by the presence of the phenolic compounds. The catechol moiety of Cat, Que, and rutin plays an essential role in concerted proton-coupled electron transfer (PCET) to HO2· derived from O2·− to give H2O2 and the corresponding o-benzoquinone radical anions. On the other hand, the presence of α-TOH causes sequential electron and proton transfers to HO2· to give H2O2 and the α-tocopheroxyl radical. These electron transfers in the presence of the phenolic compounds are inferred from the ESR spectral measurements. The DFT calculation results suggest that the O2·− scavenging reaction of the natural phenolic compounds proceeds efficiently with the one-step concerted PCET or sequential PCET mechanism.
The reactivity of 4-(E)-2-(3,5-dihydroxyphenyl)ethenylbenzene-1,2-diol (piceatannol) toward electrochemically generated superoxide radical anion (O2 •–) was investigated using electrochemistry and ...in situ controlled-potential electrolytic electron spin resonance (ESR) measurements in N,N-dimethylformamide with density functional theory (DFT) calculations. The quasireversible cyclic voltammogram of dioxygen/O2 •–, modified in the presence of piceatannol, indicated that the electrogenerated O2 •– was scavenged by piceatannol via proton-coupled electron transfer. Differences in the reactivities of piceatannol and 5-(E)-2-(4-hydroxyphenyl)ethen-1-ylbenzene-1,3-diol (trans-resveratrol) toward O2 •–, originating from the presence of the benzene-1,2-diol (catechol) moiety, were observed in the voltammograms and ESR measurements. The electrochemical and computational results show that the reaction mechanism is a concerted two-proton-coupled electron transfer (2PCET) via the catechol moiety of piceatannol. The stilbene moiety of piceatannol kinetically promotes 2PCET via its catechol moiety. These findings indicate that piceatannol is a better O2 •– scavenger than catechol and trans-resveratrol.
We report the visible‐light‐induced trifluoromethylation of arenes and heteroarenes using sodium trifluoromethanesulfinate catalyzed by anthraquinone‐2‐carboxylic acid. This reaction is a metal‐free ...trifluoromethylation of arenes and heteroarenes catalyzed by a photoredox organocatalyst. Perfluoroalkylated arenes were also produced using sodium perfluoroalkylsulfinates.
This study demonstrates the relation between the redox properties and cytotoxicity of anthraquinone derivatives with a hydroxyl and methoxy group. The redox behavior of the anthraquinone derivatives ...was initially observed via cyclic voltammetry and their characteristics were investigated using molecular orbital calculations. The cytotoxicity of the anthraquinone derivatives was then evaluated using human leukemia HL-60 and H2O2 resistant HP100 cells, and its correlation with the redox properties of these compounds was investigated. Therefore, it was suggested that the anthraquinone derivatives express cytotoxicity through H2O2 production, and that generation of the oxidized radical form influences their cytotoxicity.
Highlights • The expression levels of miR-124 were decreased in clinical colorectal cancer (CRC) and adenoma (CRA) patients' samples. • MiR-124 induced apoptosis and/or autophagic survival in human ...colon cancer cells. • MiR-124 targeted PTB1 to modulate the Warburg effect through the switching of PKM isoform expression from PKM2 to PKM1.
Reactivity of (2E)-3-(3,4-dihydroxyphenyl)prop-2-enoic acid (caffeic acid), classified as a hydroxycinnamic acid (HCA) derivative, toward electrogenerated superoxide radical anion (O2•−) was ...investigated through cyclic voltammetry, in situ electrolytic electron spin resonance spectrometry, and in situ electrolytic ultraviolet–visible spectrometry in N,N-dimethylformamide (DMF), aided by density functional theory (DFT) calculations. The quasi-reversible redox of dioxygen/O2•− is modified in the presence of caffeic acid, suggesting that O2•− is scavenged by caffeic acid through proton-coupled electron transfer. The reactivities of caffeic acid toward O2•− are mediated by the ortho-diphenol (catechol) moiety rather than by the acryloyl group, as experimentally confirmed in comparative analyses with other HCAs. The electrochemical and DFT results in DMF suggested that a concerted two-proton-coupled electron transfer mechanism proceeds via the catechol moiety. This mechanism embodies the superior kinetics of O2•− scavenging by caffeic acid.
A highly sensitive high-performance liquid chromatography method has been developed using the pre-column fluorescent derivatization of daptomycin (DAP) through cyclization of the amino group of ...ornithine with 2,3-naphthalenedialdehyde. With the proposed method, the limits of detection and quantification of DAP in murine serum were 8 and 3 nmol/L, respectively, and the calibration curve was linear across the examined dynamic range from 8 nmol/L to 1 μmol/L (n = 8, r = 0.9986). This method is suitable for animal experiments examining the side effects of DAP therapy using mice as a simple method with quantification to the order of 10 nmol/L.
It is important to evaluate the amount of daptomycin (DAP) distributed to skeletal muscles to elucidate the mechanisms related to penetration and side effects, such as myopathies. However, no attempt ...has been made to measure DAP concentrations in skeletal muscles. The study’s aim to investigate the feasibility of trypsin digestion, as a muscle sample preparation technique for the determination of DAP in murine skeletal muscle, was evaluated in conjunction with a conventional HPLC-UV analysis. Compared with trypsin digestion, DAP was less recovered from spiked skeletal muscle by the conventional extraction, including homogenization, centrifugation, and filtration, because of its incorporation into the muscle protein. On the other hand, a sample preparation technique involving enzymatic digestion employing trypsin fully recovered DAP from the spiked skeletal muscle. Based on the spike recovery assay results, we proposed an efficient muscle sample preparation method involving trypsin digestion. HPLC analysis in conjunction with the sample preparation method has successfully determined DAP concentrations of skeletal muscles collected from mice administrated subcutaneously with DAP. The proposed method is suitable for application to investigations that include animal experiments on drug migration into muscle and mechanism underlying skeletal muscle injury as a side reaction, such as myopathies, of DAP therapy.
The deuteration of N2-ethyl-2′-deoxyguanosine (Et-dG), which is a DNA adduct generated from acetaldehyde, was studied by the addition reaction of acetaldehyde-d4 to 2′-deoxyguanosine (dG) in ...deuterium oxide (D2O), with the aim to obtain an isotope internal standard for the liquid chromatography/tandem mass spectrometry (LC/MS/MS) quantitation of Et-dG. The replacement of the dG C-8 hydrogen atom by a deuteron atom took place at 50°C in D2O and afforded a mixture of Et-dG-d4 and Et-dG-d5. Et-dG-d4, which was stable in aqueous solutions, was prepared by incubating the mixture in H2O at 60°C for 48 h. The calibration curve was obtained by multiple reaction monitoring (MRM) measurements using a hydrophilic interaction chromatography–electrospray ionization–tandem mass spectrometric (HILIC/ESI-MS/MS) system between the Et-dG concentration, ranging from 1.0 × 10−10 to 4.0 × 10−9 M in the sample solutions, and the relative peak areas of Et-dG (m/z: 296.1 → 180.1) to the value of Et-dG-d4 (m/z: 300.2 → 184.2), with an internal standard showing good linearity (R2 = 0.995, n = 5).
Daptomycin is active against Staphylococcus aureus including methicillin-resistant S. aureus (MRSA), demonstrating efficacy in the treatment of infections in diabetic patients. However, daptomycin ...degrades in 5% glucose solution, and data on the efficacy of daptomycin in hyperglycemic patients are limited. Therefore, we investigated the effect of high levels of blood glucose on the efficacy and concentration of daptomycin. The efficacy of simulated human exposure to daptomycin against S. aureus was compared in a neutropenic murine thigh model, with and without hyperglycemia. A clinically isolated MRSA strain and S. aureus ATCC25923 standard strain were used. Daptomycin concentrations, in the serum and at the infected site, were preliminarily analyzed using the high-performance liquid chromatography assay. Even in hyperglycemic mice, the mean concentration of daptomycin in hyperglycemic mice was equivalent to that in untreated mice within the physiological blood glucose levels. Additionally, the efficacy of daptomycin against MRSA was equal to that observed in the untreated and hyperglycemic mice. Based on similar studies using S. aureus ATCC25923, the efficacy in hyperglycemic mice was equal to or greater than that observed in untreated mice. In conclusion, daptomycin is an alternative therapeutic option in diabetic mice with serious staphylococcal infections, regardless of blood glucose control in this animal model.
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