Derivatization,molecular docking and in vitro acetylcholinesterase inhibitory activity of glycyrrhizin as a selective anti-Alzheimer agent

Acetylcholinesterase inhibitors (AChE-Is) increase both level and duration of action of acetylcholine (ACh); thus, alleviate symptoms of Alzheimer’s disease (AD). Glycyrrhizin, is the main active compound in liquorice root. Its aglycone, glycyrrhetinic acid, has shown several beneficial pharmacological activities. This study reports the synthesis and screening of a series of glycyrrhetinic acid analogs as AChE-Is. Fourteen derivatives were prepared, of which five derivatives are recorded as new viz., 3-phenyl-carbamoyl-18β-glycyrrhetinic acid (J9), 3-acetyl-18β-glycyrrhetinic-30-anilinamide (J10), 3-acetyl-18β-glycyrrhetinic-30-ethanolamide (J11), 3-acetyl-18β-glycyrrhetinic-30-n-butylamide (J12) and 18β-glycyrrhetinic acid-30-prenyl ester (J14), in addition to nine known derivatives (J1-J8 & J13). Compounds J12, J11, J0 and J3 showed remarkable AChE-I activity with IC₅₀ values of 3.43, 5.39, 6.27 and 8.68 μM, respectively. These results are in full agreement with the docking study. The active compounds were non-cytotoxic to normal cells (WI-38).     

Active loading and tunable release of doxorubicin from block copolymer vesicles

Vesicles are spherical bilayers that offer a hydrophilic reservoir, suitable for the incorporation of water-soluble molecules, as well as a hydrophobic wall that protects the loaded molecules from the external solution. The permeability of a vesicle wall made from polystyrene can be enhanced by adding a plasticizer such as dioxane. Tuning the wall permeability allows loading and release of molecules from vesicles to be controlled. In this study, vesicles are prepared from polystyrene(310)-b-poly(acrylic acid)(36) and used as model carriers for doxorubicin (DXR), a weak amine and a widely used anticancer drug. To increase the wall permeability, different amounts of dioxane are added to the vesicle solution. A pH gradient is created across the vesicle wall (inside acidic) and used as an active loading method to concentrate the drug inside the vesicles. The results show that a pH gradient of ca. 3.8 units can enhance the loading level up to 10-fold relative to loading in the absence of the gradient. After loading, the release of DXR from vesicles is followed as a function of the wall permeability. The diffusion coefficient of doxorubicin through polystyrene (D) is evaluated from the initial slope of the release curves; the value of D ranges from 8 x 10(-17) to 6 x 10(-16) cm(2)/s, depending on the degree of plasticization of the vesicle wall.     

Synthesis of Some New Heterocycles Derived from Novel 2‐(1,3‐Dioxisoindolin‐2‐yl)Benzoyl Isothiocyanate

Novel 2‐(1,3‐Dioxisoindolin‐2‐yl)benzoyl isothiocyanate was prepared and underwent addition–cyclization reactions with some nucleophilic reagents. Simultaneous or subsequent cyclization of the obtained adducts gave a diverse range of differently sized heterocycles and thioureas. The structures of the synthesized compounds were confirmed by microanalytical and spectral data.     

Solvent effects on the aquation of chloropentammine-cobalt(III) perchlorate in ethanol-water

Summary The aquation kinetics of the chloropenta-aminecobalt(III) ion in H₂O–EtOH mixtures have been determined. A new correlation is described for calculating the chemical potential from kinetic data and molar thermodynamic excess functions for binary mixtures. The rate constants correlate well with Grunwald-Winstein solvating power Y parameter and with the dielectric constant of the medium. The data supports the D mechanism.     

Polystyrene-b-poly(acrylic acid) vesicle size control using solution properties and hydrophilic block length

Polymeric vesicles have attracted considerable attention in recent years, since they are a model for biological membranes and have versatile structures with several practical applications. In this study, we prepare vesicles from polystyrene-b-poly(acrylic acid) block copolymer in dioxane/water and dioxane/THF/water mixtures. We then examine the ability of additives (such as NaCl, HCl, or NaOH), solvent composition, and hydrophilic block length to control vesicle size. Using turbidity measurements and transmission electron microscopy (TEM) we show that larger vesicles can be prepared from a given copolymer by adding NaCl or HCl, while adding NaOH yields smaller vesicles. The solvent composition (ratio of dioxane to THF, as well as the water content) can also determine the vesicle size. From a given copolymer, smaller vesicles can be prepared by increasing the THF content in the THF/dioxane solvent mixture. In a given solvent mixture, vesicle size increases with water content, but such an increase is most pronounced when dioxane is used as the solvent. In THF-rich solutions, on the other hand, vesicle size changes only slightly with the water concentration. As to the effect of the acrylic acid block length, the results show that block copolymers with shorter hydrophilic blocks assemble into larger vesicles. The effect of additives and solvent composition on vesicle size is related to their influence on chain repulsion and aggregation number, whereas the effect of acrylic acid block length occurs because of the relationship among the block length, the width of the molecular weight distribution, and the stabilization of the vesicle curvature.     

Aquaporin-Based Biomimetic and Bioinspired Membranes for New Frontiers in Sustainable Water Treatment Technology: Approaches and Challenges

Biomimetic and bioinspired membranes are the efficient membrane technology when it comes to multiple usage scenarios, including next generations of biomaterials within the commercial separation applications, as well as, water and wastewater treatment technologies. In recent years, aquaporin biomimetic membranes for water separation have raised considerable interest. These membranes have displayed distinguished properties and outstanding performances, as diverse interactions, varying selective transport mechanisms, superior stability, maximum resistance to membrane fouling, and distinct adaptability. The biomimetic membranes have made significant contributions when it comes to water stress, environmental threats and energy. It has the potential to produce clean water more efficiently than reverse osmosis membranes (RO), while saving up to 80% of the energy used for desalination processes. More than half of the 15000 desalination plants around the world utilize RO technologies, and the implementation of biomimetic membranes on a large scale could save hundreds of millions of dollars in energy cost annually (potential savings of $1.45 million/year for 100 ML/day desalination plant). This paper discusses the interplay of the main components of aquaporin biomimetic membranes: aquaporin proteins, block copolymers for aquaporin proteins reconstitution, and polymer-based supporting structures. We focus specifically on the challenges and review recent developments on the interplay between aquaporin proteins and block copolymers. The recent efforts in embedding reconstituted aquaporin proteins in membrane designs that are based on conventional thin film interfacial polymerization techniques are evaluated. In addition, emerging challenges and opportunities for biomimetic membranes are studied from the perspective of current and future applications.     

Chemical characterization of polyphenols from Daucus muricatus growing in Algeria by RP-UHPLC-ESI-QTOF-MS/MS

In the present work, reversed phase (RP) ultra-high-performance liquid chromatography (UHPLC) coupled to quadrupole-time-of-flight (QTOF) mass spectrometry in tandem has been used for the identification of the main phenolic compounds in the aerial parts of Daucus muricatus. The characterisation of the compounds was carried out taking into account retention time, mass accurate measurements, the generated molecular formulae and fragmentation pattern. These data were contrasted with literature and databases, as well as with those of authentic standards when possible. The proposed method provided tentative identi?cation of 30 phenolic and other polar compounds, including hydroxycinnamic acid derivatives, flavonoids and hydroxybenzoic acid derivatives. As a note, hydroxycinnamic acid derivatives were found to be the most diverse phenolic class of Daucus muricatus.     

Application of thiol-olefin co-oxygenation methodology to a new synthesis of the 1,2,4-trioxane pharmacophore

[reaction: see text] Thiol-olefin co-oxygenation (TOCO) of substituted allylic alcohols generates alpha-hydroxyperoxides that can be condensed in situ with various ketones to afford a series of functionalized 1,2,4-trioxanes in good yields. Manipulation of the phenylsulfenyl group in 4a allows for convenient modification to the spiro-trioxane substituents, and we describe, for the first time, the preparation of a new class of antimalarial prodrug.     

Omriolide A and B; two new rearranged spongian diterpenes from the marine sponge Dictyodendrilla aff. retiara

Two new rearranged spongian diterpenes designated omriolide A and B were isolated from the southern Kenyan sponge Dictyodendrilla aff. retiara collected at Wasini Is., Shimoni Channel. Omriolide A possesses an octalin linked to a unique trioxatricyclo[5.2.1.0^4,10]decane ring system, forming a tricyclic ‘cap’. Omriolide B comprised a tricyclo[5.4.0.0^2,4]undecane linked to a dioxabicyclo[3.3.0]octane. The structures of both diterpenes were elucidated by interpretation of MS results and, mainly, 1D and 2D NMR spectra.     

A chemiluminescence sensor for the determination of hydrogen peroxide

A chemiluminescence one-shot sensor for hydrogen peroxide is described. It is prepared by immobilization of cobalt chloride and sodium lauryl sulphate in hydroxyethyl cellulose matrix cast on a microscope cover glass. Luminol, sodium phosphate and the sample are mixed before use and applied on the membrane by a micropipette. The calibration graph is linear in the range 20-1600 μg/L, and the detection limit of the method (3σ) is 9 μg/L. A relative standard deviation of 4.5% was obtained for 100 μg/L H₂O₂ (n = 11). The sensor has been applied successfully to the determination of hydrogen peroxide in rainwater.