Naturally Available Flavonoid Aglycones as Potential Antiviral Drug Candidates against SARS-CoV-2

Flavonoids are important secondary plant metabolites that have been studied for a long time for their therapeutic potential in inflammatory diseases because of their cytokine-modulatory effects. Five flavonoid aglycones were isolated and identified from the hydrolyzed aqueous methanol extracts of Anastatica hierochuntica L., Citrus reticulata Blanco, and Kickxia aegyptiaca (L.) Nabelek. They were identified as taxifolin (1), pectolinarigenin (2), tangeretin (3), gardenin B (4), and hispidulin (5). These structures were elucidated based on chromatographic and spectral analysis. In this study, molecular docking studies were carried out for the isolated and identified compounds against SARS-CoV-2 main protease (Mpro) compared to the co-crystallized inhibitor of SARS-CoV-2 Mpro (α-ketoamide inhibitor (KI), IC₅₀ = 66.72 µg/mL) as a reference standard. Moreover, in vitro screening against SARS-CoV-2 was evaluated. Compounds 2 and 3 showed the highest virus inhibition with IC₅₀ 12.4 and 2.5 µg/mL, respectively. Our findings recommend further advanced in vitro and in vivo studies of the examined isolated flavonoids, especially pectolinarigenin (2), tangeretin (3), and gardenin B (4), either alone or in combination with each other to identify a promising lead to target SARS-CoV-2 effectively. This is the first report of the activity of these compounds against SARS-CoV-2.     

Formation and crystallographic orientation study of quasicrystal, 2/1 and 1/1 approximants in Cd–Mg–Y system using electron backscatter diffraction (EBSD)

A partial isothermal ternary phase diagram of the Cd–Mg–Y system including icosahedral quasicrystal (i-QC) and 1/1 approximant (APP) was obtained at 673?K. The stability of the i-QC and APPs in terms of composition and temperature was studied, as a result of which the 2/1 APP phase was discovered at 773?K. Moreover, the i-QC phase was found to be stable at lower Y concentrations of ～12–13?at.%, as compared to the 1/1 APP, which showed ～15–16?at.% Y. Single i-QC, 2/1 and 1/1 APP grains were also synthesized applying centrifuging system. Electron backscatter diffraction (EBSD) characterization of the obtained i-QC and APPs revealed almost the same Kikuchi patterns for the i-QC and 2/1 APP, indicating high resemblance of their structures. However, the Kikuchi pattern acquired from the 1/1 APP was distinguishable from the one obtained from the i-QC as it showed split bands. The occurrence of the split bands was associated with significant deviation from a perfect icosahedral symmetry. This was also confirmed by analysing calculated electron diffraction and Kikuchi patterns along pseudo-five-fold axes of the 2/1 and 1/1 APPs. Finally, orientation relationships between the i-QC, 1/1 APP and α-Mg were investigated by analysing acquired EBSD Kikuchi patterns from the respective domains. Accordingly, three perpendicular two-fold axes of the i-QC and {100} axes of the 1/1 APP occur along three mutually orthogonal {0001}, {10-10} and {11-20} axes of the α-Mg.     

Annealing of heavy ion tracks in cellulose nitrate plastic track detectors

The effect of heat treatment on the latent tracks in cellulose nitrate plastic track detectors has been studied. The bulk etch rate increases with annealing temperature while the track diameters of different ions in cellulose nitrate decrease with increase in annealing time and temperature. Experimental results show that for heavier ions higher temperatures are needed for their complete erasure. The track length and track etch rate are decreased by the application of heat. Experiments reveal that annealing reduces track density. The vertical tracks are more stable than the oblique tracks and require higher temperature for their complete erasure.     

Langevin dynamics simulations of phase separation in a one-component system

Langevin dynamics computer simulations have been performed for a two-dimensional Lennard-Jones fluid quenched into the coexistence region of its liquid-vapor phase diagram. For late stages of the phase-separation process, the average radius of the liquid clusters is found to grow proportional to (time)^1/4. This growth law is analyzed theoretically and compared to recent molecular dynamics and Monte Carlo results. Details of the different simulation methods are critically discussed.     

Kinetics of isothermal decomposition of γ-irradiated and unirradiated Co(II) succinato complex

A kinetic study of the dehydration and decomposition of -irradiated and unirradiated Na₂[Co(C₄H₄O₄)₂]·7H₂O has been studied using isothermal and dynamic thermogravimetric methods. The thermal dehydration occurs in one step regulated by a random nucleation model (A₃), while the decomposition of anhydrous salt is controlled by a phase boundary controlled model (R₃). The kinetic parameters obtained at three heating rates are in good agreement; however, the values of the kinetic parameters estimated isothermally are slightly different from those estimated dynamically. Irradiation enhanced both the dehydration and the decomposition reactions but did not modify their mechanisms. The activation energy decreases as the irradiation dose increases.

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Zusammenfassung Unter Anwendung von isothermen und dynamischen thermogravimetrischen Methoden wurde eine kinetische Untersuchung der Dehydratation und der Zersetzung von -bestrahltem und unbestrahltem Na₂[Co(C₄H₄O₄)₂]·7H₂O durchgeführt. Die thermische Dehydratation erfolgt in einem Schritt, bestimmt durch ein Random-Keimbildungsmodell (A₃), während die Zersetzung der wasserfreien Salze durch ein phasengrenzenkontrolliertes Modell bestimmt wird (R₃). Die bei drei Aufheizgeschwindigkeiten erhaltenen kinetischen Parameter stehen in guter Übereinstimmung; jedoch weichen die isotherm geschätzten kinetischen Parameter etwas von den dynamisch ermittelten ab. Bestrahlung mehrt sowohl die Dehydratations- als auch die Zersetzungsreaktionen, beläßt deren Mechanismus jedoch unverändert. Die Aktivierungsenergie sinkt mit zunehmender Strahlungsdosis.

     

Immobilization of palladium nanoparticles as a recyclable heterogeneous catalyst for the Suzuki–Miyaura coupling reaction

This work describes the synthesis of Pd nanoparticles that are stabilized on CaAl-layered double hydroxide functionalized with Tris (tris(hydroxymethyl)aminomethane). The synthesized catalyst is characterized by several different analyses and has been successfully applied to the Suzuki–Miyaura reaction.     

Production, purification, and biochemical characterization of two beta-glucosidases from Sclerotinia sclerotiorum

The filamentous fungus Sclerotinia sclerotiorum produces beta-glucosidases in liquid culture with a variety of carbon sources, including cellulose (filter paper), xylan, barley straw, oat meal, and xylose. Analysis by native polyacrylamide gel electrophoresis (PAGE) followed by an activity staining with the specific chromogenic substrate, 5-bromo 4-chloro 3-indolyl beta-1,4 glucoside (X-glu) showed that two extracellular beta-glucosidases, designated as beta-glu1 and beta-glu2, were in the filter paper culture filtrate. Only one enzyme designated as beta-glu x was revealed by the same method in the xylose culture filtrate. Beta-glu1 and beta-glu2 were purified to homogeneity. The purification procedure consist of a common step of anion-exchange chromatography on DEAE-Sepharose CL6B, both high-performance liquid chromatography (HPLC) anion-exchange and gel filtration columns for beta-glu1 and only HPLC gel filtration for beta-glu2. Beta-glu1 has a molecular mass of 196 kDa and 96.5 kDa, as estimated by gel filtration and sodium dodecyl sulfate (SDS)-PAGE, respectively, suggesting that the native enzyme may consist of two identical subunits. The same analysis showed that beta-glu2 is a monomeric protein with an apparent molecular mass of about 76.5 kDa. Beta-glu1 and beta-glu2 hydrolyses PNPGlc and cellobiose, with apparent Km values respectively for PNPGlc and cellobiose of 0.1 and 1.9 mM for beta-glu1 and 2.8 and 8 mM for beta-glu2. Both enzymes exhibit the same temperature and pH optima for PNPGlc hydrolysis (60 degrees C and pH 5.0). beta-glu1 was stable over a pH range of 3-8 and kept 50% of its activity after 30 min of heating at 60 degrees C without substrate. It was further characterized by studying the effect of some cations and various reagents on its activity.     

Benzimidazole condensed ring systems. 1. Syntheses and biological investigations of some substituted pyrido[1,2-a]benzimidazoles

The synthesis of some substituted 3-hydroxy-1-oxo-1H,5H-pyrido[1,2-a]benzimidazole-4-carbonitriles and 4-ethyl carboxylates 3 and their 0- and N-dialkyl derivatives 5,6 is described. 3-Ethoxy-5-ethyl-2-phenyl-1H,5H-pyrido[1,2-a]benzimidazol-1-one 7 was obtained during the course of ethylating the parent ester 3t with triethyl phosphate. Chlorination of 3 with phosphorus oxychloride afforded the corresponding 1,3-dichloropyrido[1,2-a]benzimidazoles 8 which were converted to a variety of azido, amino, morpholino and methoxy derivatives of the system. The synthesis of the indolopyridobenzimidazole 15 is also described. Two compounds exhibited in vitro antibacterial activity. Many compounds were screened for antileukemic, antimicrobial, herbicidal and plant antifungal potencies but were inactive.     

Production, purification, and biochemical characterization of two β-glucosidases from Sclerotinia sclerotiorum

The filamentous fungus Sclerotinia sclerotiorum prudces ß-glucosidases in liquid culture with a variety of carbon sources, including cellulose (filter paper), xylan, barley straw, oat meal, and xylose. Analysis by native polyacrylamide gel electrophoresis (PAGE) followed by an activity staining with the specific chromogenic substrate, 5-bromo 4-chloro 3-indolyl ß-1,4 glucoside (X-glu) showed that two extracellular β-glucosidases, designated as ß-glul1 and \-glu2, were in the filter paper culture filtrate. Only one enzyme designated as ß-glus was revealed by the same method in the xylose culture filtrate. ß-glu1 and ß-glu2 were purified to homogeneity. The purification procedure consist of a common step of anion-exchange chromatography on DEAE-Sepharose CL6B, both high-performance liquid chromatography (HPLC) anion-exchange and gel filtration columns for ß-glu1 and only HPLC gel filtration for ß-glu2. ß-glu1 has a molecular mass of 196 kDa and 96.5 kDa, as estimated by gel filtration and sodium dodecyl sulfate (SDS)-PAGE, respectively, suggesting that the native enzyme may consist of two identical subunits. The same analysis showed that ß-glu2 is a monomeric protein with an apparent molecular mass of about 76.5 kDa. ß-glu1 and ß-glu2 hydrolyses PNPG1c and cellobiose, with apparent K _m values respectively for PNPGlc and cellobiose of 0.1 and 1.9 mM for ß-glu1 and 2.8 and 8 mM for ß-glu2. Both enzymes exhibit the same temperature and pH optima for PNPG1c hydrolysis (60°C and pH 5.0). ß-glu1 was stable over a pH range of 3–8 and kept 50% of its activity after 30 min of heating at 60°C without substrate. It was further characterized by studying the effect of some cations and various reagents on its activity.     

Benzimidazole condensed ring systems. 2. New synthesis of substituted 1-oxo-1H,5H-pyrido[1,2-a]benzimidazole-4-carbonitriles and related derivatives

The synthesis of some 3-substituted and 2,3-disubstituted-1-oxo-1H,5H-pyrido[1,2-a]benzimidazole-4-carbo-nitriles 5,6 by fusing 1H-benzimidazole-2-acetonitrile 1 with some β-keto esters 2,4 in the presence of ammonium acetate or with ethyl β-aminocrotonate 3 is described. The tricyclic compounds were converted to their N-5 methyl of N-5 ethyl derivatives 8,9. Vilsmeir-Haack formylation of 3-methyl-1-oxo-1H,5H-pyrido[1,2-a]-benzimidazole-4-carbonitrile 5a afforded its 2-formyl derivative 10. Chlorination of 5 and 6 with phosphorus oxychloride yielded the respective 1-chloropyrido[1,2-a]benzimidazole-4-carbonitriles 11,12 which were utilized to prepare the 1-azido, 1-amino, 1-piperidino and 1-methoxy derivatives of the ring system. Compound 11a exhibited strong in vitro activity against S. aureus. Four compounds were screened against P-388 lymphocytic leukemia in mice but were inactive.