Autoxidation Enhances Anti-Amyloid Potential of Flavone Derivatives

The increasing prevalence of amyloid-related disorders, such as Alzheimer’s or Parkinson’s disease, raises the need for effective anti-amyloid drugs. It has been shown on numerous occasions that flavones, a group of naturally occurring anti-oxidants, can impact the aggregation process of several amyloidogenic proteins and peptides, including amyloid-beta. Due to flavone autoxidation at neutral pH, it is uncertain if the effective inhibitor is the initial molecule or a product of this reaction, as many anti-amyloid assays attempt to mimic physiological conditions. In this work, we examine the aggregation-inhibiting properties of flavones before and after they are oxidized. The oxidation of flavones was monitored by measuring the UV-vis absorbance spectrum change over time. The protein aggregation kinetics were followed by measuring the amyloidophilic dye thioflavin-T (ThT) fluorescence intensity change. Atomic force microscopy was employed to image the aggregates formed with the most prominent inhibitors. We demonstrate that flavones, which undergo autoxidation, have a far greater potency at inhibiting the aggregation of both the disease-related amyloid-beta, as well as a model amyloidogenic protein—insulin. Oxidized 6,2′,3′-trihydroxyflavone was the most potent inhibitor affecting both insulin (7-fold inhibition) and amyloid-beta (2-fold inhibition). We also show that this tendency to autoxidize is related to the positions of the flavone hydroxyl groups.

Antiradical activity of novel 4-amino-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-thiol derivatives

The process of studying free radicals began in the middle of the last century (the free radical theory of aging in 1956). Multiple studies have revealed the effect of free radicals on the cells of the body and the development of various diseases, such as diabetes, autoimmune diseases, diseases of the nervous system, and others. As a result, the term antioxidant has emerged, compounds that reduce and prevent the effects of free radicals. Most of the newly synthesized substances are studied for their antiradical properties. 1,2,4-Triazole derivatives are no exception, which has already proven themselves as biologically active compounds. The aim of this work was the investigation antiradical activity among 4-amino-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-thiol derivatives. Materials and methods. Previously synthesized 4-amino-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-thiol derivatives were used as test compounds. The research of antiradical activity was based on the interaction between 4-amino-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-thiol derivatives and 2,2-diphenyl-1-picrylhydrazyl (DPPH) in vitro. DPPH is a stable free radical. The color of its alcoholic solutions were intense purple (λmax = 517 nm). When DPPH interacted with compounds that were capable of scavenging free radicals, it produced products. These products are yellow in color and do not absorb light of the aforementioned wavelength. The study was carried out according to the method. Results. The antiradical activity of 10 new 4-amino-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-thiol derivatives was studied. Most of the test compounds show antiradical activity against DPPH. Compound 1 was the most active at a concentration of 1 × 10-3 M and the antiradical effect was close to ascorbic acid. Conclusions. The most active compound is 4-amino-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-thiol, which in a concentration of 1 × 10-3 M has an antiradical effect in 88.89 %. When reducing the concentration to 1 × 10-4 M, also reduces the antiradical activity to 53.78 %. Some conclusions are drawn regarding the “structure – effect” dependence between 4-amino-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-thiol derivatives: – the introduction of 4-fluorobenzylidene radical (compound 2) into the 4-amino-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-thiol molecule results in a slight decrease in activity; – the introduction of 2-hydroxybenzylidene radical (compound 3) into initial molecule results a high antiradical effect, which hardly changes with decreasing concentration; – transformation to 2-((5-(thiophen-2-ylmethyl)-4-((R)amino)-4H-1,2,4-triazol-3-yl)thio)acetic acid has almost no effect on antiradical activity, except for compound 9 (the antiradical effect is reduse).

Degradation of micropollutant cephalexin by ultraviolet (UV) and assessment of residual antimicrobial activity of transformation products

Cephalexin (CEX) is an antibiotic commonly used to treat bacterial infections in humans and animals. However, it can be considered a micropollutant. Thus, this study evaluated the degradation of CEX using ultraviolet irradiation (UV-C) and analyzed the by-products as well as their residual antimicrobial activity. A reactor with a mercury vapor lamp was used for the degradation. Irradiated CEX solution were collected over a period of 4 h and analyzed by High Performance Liquid Chromatography coupled with Mass Spectrometry. For the residual antimicrobial activity the susceptibility test was performed by broth microdilution against Staphylococcus aureus and Escherichia coli microorganisms. It was found that CEX, after treatment, generated a metabolite with a mass of 150 m/z in 15 min, and a 4- and 8-fold increase in the minimum inhibitory concentration of the drug against S. aureus and E. coli, could be observed, respectively, after 20 min. Therefore, this treatment proved to be effective in the degradation of CEX, being able to degrade 81% of the initial molecule of the drug in 20 min. Furthermore, the antimicrobial activity of the CEX solution decreased as the irradiation time increased, indicating loss of antimicrobial function of the initial CEX molecule and the resulting by-products.

SPR Effect Controlled by an Electric Field in a Tapered Optical Fiber Surrounded by a Low Refractive Index Nematic Liquid Crystal

This paper presents the influence of a thin metal layer deposition on the surface of a tapered optical fiber surrounded by a low liquid crystal, on light propagation inside the taper structure. In this research, three types of liquid crystal cells were under investigation: orthogonal, parallel, and twist. They differed by the rubbing direction of the electrodes in relation to the fiber axis determining the initial molecule arrangement inside the cell. Gold films with thickness d = 30 nm were deposited on the tapered fiber surface in the tapered waist area. Cells including a tapered optical fiber with no metallic layer were also examined and presented as a reference. All measurements were performed at room temperature for a different steering voltage U from 0 to 200 V, with and without any amplitude modulation with a frequency f = 5 Hz, and the wavelength λ range from 550 to 1200 nm. As a result, the resonant peaks were obtained, which depends on a liquid crystal cell type and steering voltage, as well. This paper shows the possibility of sensing the change of applied voltage by the constructed system. During measurements, additional effects as signal overlapping and intermodal interference were observed reducing measured voltage value. In the future, the improved, similar systems that will have a better response could be used as a sensor of factors to which liquid crystal (LC) will be sensitive, especially temperature and electric field.

Фрагментация молекулы глютамина электронным ударом

Using the mass-spectrometric analysis technique, formation of the ionic products of the single and dissociative ionization of the glutamine molecule (C5H10N2O3) at its interaction with the low (70 eV) and high (11.5 MeV) energy electrons has been studied. The experimental mass-spectra of the above molecule measured at different irradiation doses (5, 10 and 20 kGy) and the near-threshold areas of the ionic fragment yield functions have been analyzed, the absolute ion fragment appearance energies have been found. The three-electrode electron gun and the electron accelerator (microtron) were used as the electron beam sources. The analysis of the behaviour of the measured glutamine molecule mass-spectra irradiated at the above doses demonstrates, as compared to the irradiated molecule mass-spectrum, that the high-energy irradiation of the initial molecule results in the irreversible changes of its structure.

Antioxidant action and cytotoxicity on HeLa and NIH-3T3 cells of new quercetin derivatives

ABSTRACT Quercetin is a natural polyphenol with proven health beneficial activities. In this study 15 new quercetin derivatives were prepared with the aim to enhance their bioavailability. Modification of their physicochemical properties could herewith improve the action in cells. The prepared compounds were tested for their antioxidant and cytotoxic activity. The ability to scavenge free radicals as well as ferric reducing antioxidant power of the new derivatives was not better than that of unmodified quercetin. But for acetylated esters a better cytotoxic activity was found on human cervical cancer cells HeLa than for the initial molecule. The best effect revealed chloronaphtoquinone quercetin (IC50=13.2 μM). For this compound comparable cytotoxic action on non-cancer murine fibroblast cells was detected (IC50=16.5 μM). The obtained results indicate that appropriate lipophilization of the quercetin molecule could improve its cytotoxic action in cells, probably due to its enhanced bioavailability

Formation of Gas Phase Boron and Carbon-Containing Molecular Species at High Temperatures

The formation of gas phase boron and carbon containing molecular species at high temperatures (thermal plasma) is investigated theoretically, by computing the equilibrium composition of the gas mixture containing boron, carbon, hydrogen and argon. The calculations are performed for the temperature range between 500 and 6000 K, B/C=1 and 2 and for the total pressure in the system of 1 bar. Use is made of the fact that the thermal plasma is plasma in local thermodynamic equilibrium, which makes possible theoretical determination (by employing the Gibbs free energy data for the compounds present in the system) of its equilibrium composition. From the calculated compositions of the investigated gas systems, presented in this paper, it was concluded that the initial molecule for cluster formation, as a connection between individual molecules and the solid state, in the case of the synthesis of solid boron carbide by means of thermal plasma should be the B2C molecule.

A Simulation Method for Spreading Dynamics of Molecularly Thin Lubricant Films on Magnetic Disks Using Bead-Spring Model

An effective simulation technique for describing the spreading properties of molecularly thin lubricant films on magnetic disks has been developed. We propose a molecular precipitation method that can simulate initial molecule arrangement of the films dip-coated onto the disks. Reptation and Rouse models as the model of the molecular motion, and molecular insertion and molecular precipitation methods as the method for putting molecules in initial positions were compared. From the results of the spreading profiles and diffusion coefficients, it has been revealed that the molecular precipitation method combined with the Rouse model is effective in simulating the spreading of the lubricant films.