Benzimidazole tethered thioureas as a new entry to elastase inhibition and free radical scavenging: Synthesis,molecular docking,and enzyme inhibitory kinetics

The porcine pancreatic elastase inhibition and free-radical scavenging play a crucial role in age progression. All the series of 10 newly synthesized benzimidazole thioureas ( 4a-j ) were assessed for elastase inhibition and radical scavenging activity to identify the suitable anti-aging ingredient for cosmetics products. The compounds 4e , 4f , 4g , and 4h showed inhibition better than the standard, while compound 4f showed the most significant elastase inhibition with the IC₅₀ value of 1.318 ± 0.025 μM compared with oleanic acid IC₅₀ 13.451 ± 0.014 used ±1.989 and 41.563 ± 0.824, respectively, as standard. Molecular docking studies were performed and the compound 4f showed binding energy of 7.2 kcal/mol. Kinetics studies revealed inhibition of the pancreatic elastase in a competitive manner. The relative binding energy and structure activity relationship (SAR) identified compound 4f as an effective inhibitor of porcine pancreatic elastase. Compounds 4e and 4i showed remarkable free-radical scavenging activity with SC₅₀ values of 26.421.     

Kinetic,isotherm, and mechanism investigations of the removal of nitrate and nitrite from water by the synthesized hydrotalcite Mg–Al

Research on Chemical Intermediates - The objective of this work is to test the effectiveness of hydrotalcite as an adsorbent for the retention of nitrate and nitrite ions and to study the influence...     

NMR studies of interactions of new CB2 cannabinoid receptor ligands with cyclodextrins hosts. Correlation with micellar electrokinetic chromatography and reversed phase high performance liquid chromatography

Three selective CB₂ cannabinoid receptor ligands have recently been discovered to be promising anti-inflammatory agents but their low water solubility hinder their per os administration. The popularity of the cyclodextrins, from a pharmaceutical standpoint lies on their ability to interact with poorly water-soluble drugs and improve their solubility. Herein, three experimental approaches for calculating the stability constant of complexes between the selective CB₂ ligands and either the β-CD or the HP-β-CD, were tested: nuclear magnetic resonance, micellar electrokinetic chromatography and high performance liquid chromatography in reversed phase. In NMR studies the calculated K values were relatively high and were between 1486 and 3571 M^?1 with β-CD. With HP-β-CD they were between 1203 and 2650 M^?1. Concerning the two others techniques the K values were found lower. In MECK studies with β-CD they were between 308 and 792 M^?1 and with HP-β-CD between 124 and 764 M^?1. Finally in RP-HPLC studies with β-CD, they were between 539 and 1144 M^?1 and with HP-β-CD between 196 and 396 M^?1. These calculated constants suggest that a complexation phenomenon occurs. A model for inclusion of one of the CB₂ ligands in the β-CD was then proposed from molecular modeling studies.     

Physico-Chemical and Phytochemical Characterization of Moroccan Wild Jujube “Zizyphus lotus (L.)” Fruit Crude Extract and Fractions

Wild jujube “Ziziphus lotus (L.) Desf.” belongs to the Rhamnaceae family and is a traditionally herbaceous medicinal plant. It is very common in arid and semi-arid regions and is currently used for its antidiabetic, sedative, analgesic, anti-inflammatory and hypoglycemic activities. The aim of the present work was to characterize the physico-chemical properties and the phytochemical profile of wild jujube sample collected from the Guercif region, in order to determine the polyphenolic compounds and the antioxidant ability Analyses were carried out directly after the harvest for the determination of pH, refractive index, total soluble solid (°Brix), dry matter, sugar/acidity, total sugars, reducing sugars, as well as lipid and protein content. Results showed that the investigated fruit is acidic (pH 4.9 ± 0.23) and rich in sugars (80.2 g/100 g ± 3.81). The GC-MS analysis of the fruit revealed a number of volatile compounds, as many as 97, belonging to different chemical classes. The HPLC-DAD-ESI/MS analysis showed the presence of a total of 20 polyphenolic compounds in both EtOAc and MeOH-water extracts. Among them, p-Hydroxybenzoic acid was the most abundant in the EtOAc extract (185.68 µg/100 mg ± 0.5) whereas Quercetin 3-O-rhamnoside-7-O-glucoside was found in higher amounts in the MeOH-water extract (25.40 µg/100 mg ± 0.5). These components have medical interest, notably for human nutrition, as well as health benefits and therapeutic effects. Therefore, Moroccan jujube “Zizyphus lotus (L.)” fruit may have potential industrial applications for food formulations.     

2-Hydroxyestradiol Overcomes Mesenchymal Stem Cells-Mediated Platinum Chemoresistance in Ovarian Cancer Cells in an ERK-Independent Fashion

Ovarian cancer (OC) is the second most common type of gynecological malignancy. Platinum (Pt)-based chemotherapy is the standard of care for OC, but toxicity and acquired chemoresistance has proven challenging. Recently, we reported that sensitivity to platinum was significantly reduced in a co-culture of OC cells with MSC. To discover compounds capable of restoring platinum sensitivity, we screened a number of candidates and monitored ability to induce PARP cleavage. Moreover, we monitored platinum uptake and expression of ABC transporters in OC cells. Our results showed that 2-hydroxyestradiol (2HE2), a metabolite of estradiol, and dasatinib, an Abl/Src kinase inhibitor, were significantly effective in overcoming MSC-mediated platinum drug resistance. Dasatinib activity was dependent on ERK1/2 activation, whereas 2HE2 was independent of the activation of ERK1/2. MSC-mediated platinum drug resistance was accompanied by reduced intracellular platinum concentrations in OC cells. Moreover, MSC co-cultured with OC cells resulted in downregulation of the expression of cellular transporters required for platinum uptake and efflux. Exposure to 2HE2 and other modulators resulted in an increase in intracellular platinum concentrations. Thus, 2HE2 and dasatinib might act as sensitizers to restore platinum drug sensitivity to OC cells and thus to limit TME-mediated chemoresistance in OC.     

Antibacterial Mechanisms of Zinc Oxide Nanoparticle against Bacterial Food Pathogens Resistant to Beta-Lactam Antibiotics

The increase in β-lactam-resistant Gram-negative bacteria is a severe recurrent problem in the food industry for both producers and consumers. The development of nanotechnology and nanomaterial applications has transformed many features in food science. The antibacterial activity of zinc oxide nanoparticles (ZnO NPs) and their mechanism of action on β-lactam-resistant Gram-negative food pathogens, such as Escherichia coli, Pseudomonas aeruginosa, Salmonella typhi, Serratia marcescens, Klebsiella pneumoniae, and Proteus mirabilis, are investigated in the present paper. The study results demonstrate that ZnO NPs possesses broad-spectrum action against these β-lactamase-producing strains. The minimal inhibitory and minimal bactericidal concentrations vary from 0.04 to 0.08 and 0.12 to 0.24 mg/mL, respectively. The ZnO NPs elevate the level of reactive oxygen species (ROS) and malondialdehyde in the bacterial cells as membrane lipid peroxidation. It has been confirmed from the transmission electron microscopy image of the treated bacterial cells that ZnO NPs diminish the permeable membrane, denature the intracellular proteins, cause DNA damage, and cause membrane leakage. Based on these findings, the action of ZnO NPs has been attributed to the fact that broad-spectrum antibacterial action against β-lactam-resistant Gram-negative food pathogens is mediated by Zn²⁺ ion-induced oxidative stress, actions via lipid peroxidation and membrane damage, subsequently resulting in depletion, leading to β-lactamase enzyme inhibition, intracellular protein inactivation, DNA damage, and eventually cell death. Based on the findings of the present study, ZnO NPs can be recommended as potent broad-spectrum antibacterial agents against β-lactam-resistant Gram-negative pathogenic strains.     

Optimization of a New Extraction Technique for Analysis of Verbenone and cis-Verbenol in Pine Seeds

Results from a systematic study of the factors affecting extraction of cis-verbenol and verbenone from pine seeds are presented. Five extraction conditions were investigated: extraction solvent, method of extraction, extraction temperature, volume of solvent, and the ratio of the mass of sample to the amount of extraction solvent. The resulting optimized method uses magnetic-stirring-assisted extraction of pine seeds (5 g) with ethyl acetate (75 mL) for 20 min, at room temperature. RSDs were less than 5% for both compounds. GC–FID was used for quantification of cis-verbenol and verbenone in the extracts.     

Equilibrium and kinetic studies for the adsorption of benzene and toluene by graphene nanosheets: a comparison with carbon nanotubes

In this study, graphene nanosheets (GNSs) were adopted as an adsorbent to investigate their characterizations and performance for adsorbing benzene and toluene in aqueous solutions. In order to determine the best fit model for each considered system, nonlinear regressions were used. Experimental data of adsorption were corroborated by the combined Langmuir–Freundlich (Sips) models for the isotherms and pseudo‐first‐order model for the kinetics. As a result, GNSs displayed high affinity to the aromatic hydrocarbons such as benzene and toluene. The high affinity was dominated by π–π interactions to the flat surface and the sieving effect of the powerful groove regions formed by wrinkles on GNS's surfaces. Hydrophobic properties and molecular sizes of benzene and toluene affected the adsorption of GNS. In addition, the favorable adsorption of toluene possibly was due to the increase in the molecular weight, decrease in the solubility, and the increase in the boiling point. A comparative study on the benzene and toluene adsorption revealed that favorable adsorption of GNSs compared with that of carbon nanotubes was consistent with the order of physical properties such as specific surface area and pore's volume. Copyright © 2016 John Wiley & Sons, Ltd.     

Phytochemical and In Silico ADME/Tox Analysis of Eruca sativa Extract with Antioxidant,Antibacterial and Anticancer Potential against Caco-2 and HCT-116 Colorectal Carcinoma Cell Lines

Eruca sativa Mill. (E. sativa) leaves recently grabbed the attention of scientific communities around the world due to its potent bioactivity. Therefore, the present study investigates the metabolite profiling of the ethanolic crude extract of E. sativa leaves using high resolution-liquid chromatography-mass spectrometry (HR-LC/MS), including antibacterial, antioxidant and anticancer potential against human colorectal carcinoma cell lines. In addition, computer-aided analysis was performed for determining the pharmacokinetic properties and toxicity prediction of the identified compounds. Our results show that E. sativa contains several bioactive compounds, such as vitamins, fatty acids, alkaloids, flavonoids, terpenoids and phenols. Furthermore, the antibacterial assay of E. sativa extract showed inhibitory effects of the tested pathogenic bacterial strains. Moreover, the antioxidant activity of 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydrogen peroxide (H₂O₂) were found to be IC₅₀ = 66.16 μg/mL and 76.05 μg/mL, respectively. E. sativa also showed promising anticancer activity against both the colorectal cancer cells HCT-116 (IC₅₀ = 64.91 μg/mL) and Caco-2 (IC₅₀ = 83.98 μg/mL) in a dose/time dependent manner. The phytoconstituents identified showed promising pharmacokinetics properties, representing a valuable source for drug or nutraceutical development. These investigations will lead to the further exploration as well as development of E. sativa-based nutraceutical products.     

Heavy-atom kinetic isotope effects,cocatalysts, and the propagation transition state for polymerization of 1-hexene using the rac-(C(2)H(4)(1-indenyl)(2))ZrMe(2) catalyst precursor

Using 13C NMR techniques, the 12C/13C kinetic isotope effects (KIEs) for the polymerization of 1-hexene catalyzed by rac-(C2H4(1-indenyl)2)ZrMe2 in the presence of four different cocatalysts (tris(pentfluorophenyl)borane, tris(pentafluorophenyl)alane, anilinium tetrakis(pentafluorophenyl)borate, and methylalumoxane) have been determined. All cocatalysts yield similar KIEs within experimental uncertainty, with values of 1.009(1) and 1.017(2) at C1 and C2, respectively. Ab initio DFT computational modeling of the polymerization KIE indicates that alkene binding to the catalyst must be reversible, with the majority of the KIE developing in the subsequent migratory insertion reaction.