Therapeutic Targeting of the NRF2 Signaling Pathway in Cancer

Cancer is one of the most fatal diseases with an increasing incidence and mortality all over the world. Thus, there is an urgent need for novel therapies targeting major cancer-related pathways. Nuclear factor-erythroid 2-related factor 2 (NRF2) and its major negative modulator Kelch-like ECH-associated protein 1 (KEAP1) are main players of the cellular defense mechanisms against internal and external cell stressors. However, NRF2/KEAP1 signaling pathway is dysregulated in various cancers, thus promoting tumor cell survival and metastasis. In the present review, we discuss the mechanisms of normal and deregulated NRF2 signaling pathway focusing on its cancer-related functions. We further explore activators and inhibitors of this pathway as cancer targeting drug candidates in order to provide an extensive background on the subject.     

Uniformly Oriented Zeolite ZSM‐5 Membranes with Tunable Wettability on a Porous Ceramic

Facile fabrication of well‐intergrown, oriented zeolite membranes with tunable chemical properties on commercially proven substrates is crucial to broadening their applications for separation and catalysis. Rationally determined electrostatic adsorption can enable the direct attachment of a b‐oriented silicalite‐1 monolayer on a commercial porous ceramic substrate. Homoepitaxially oriented, well‐intergrown zeolite ZSM‐5 membranes with a tunable composition of Si/Al=25–∞ were obtained by secondary growth of the monolayer. Intercrystallite defects can be eliminated by using Na⁺ as the mineralizer to promote lateral crystal growth and suppress surface nucleation in the direction of the straight channels, as evidenced by atomic force microscopy measurements. Water permeation testing shows tunable wettability from hydrophobic to highly hydrophilic, giving the potential for a wide range of applications.     

Synthesis and In-Vitro Antimicrobial Activity of Novel Aminophosphinic Acids Containing Cyclobutane and 1,3-Thiazole

Abstract

The compounds {[4-(3-methyl-3-aryl(mesityl-phenyl-tetralino)cyclobutyl)-1,3-thiazol-2-yl]amino}(aryl)methyl-phosphinic acids 2a–l were prepared by condensation of 2-amino-4-(3-aryl(mesityl-phenyl-tetralino)-3-methylcyclobutyl) thiazoles 1a–c with various aromatic aldehydes and hypophosphorous acid through a one-pot reaction. The characterizations of these compounds were obtained by elemental analyses, infrared (IR) spectra, and ¹H, ¹³C, and ³¹P NMR (nuclear magnetic resonance) techniques. The synthesized compounds were tested in vitro against one Gram-positive and two Gram-negative bacterial strains, one mycobacterial strain, and a fungus Candida albicans. Compound 2f showed significant activity against Staphylococcus aureus, whereas the others had no remarkable activity on this strain. Compound 2g was found to be more active than the others against Mycobacterium fortuitum at an MIC (minimum inhibitory concentration) value of 32 μg/mL. The antibacterial and antifungal activities of 2a–l were also compared with various standard drugs.

[Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements for the following free supplemental resource: Biological Activities. Table S1. Figures S1–S6.]

GRAPHICAL ABSTRACT      

Synthesis,antioxidant and antitumor activities of some of new cyclobutane containing triazoles derivatives

Abstract

Thiosemicarbazides (2a–e) were obtained by the interaction of furan-2-carboxylic acid hydrazide (1) with five different isothiocyanate (RNCS) derivatives. By addition of KOH to the reaction medium, ethyl, allyl, phenyl and benzyl, p-tolyl substituted 1,2,4-triazoles (3a–e) were obtained. 3a–e were dissolved in dry acetone containing K₂CO₃ in the presence of 2-chloro-1-(3-methyl-3-mesitylcyclobutyl) ethanone (4) to give 3,4,5-trisubstituted 1,2,4-triazole sulfanyl compounds containing a cyclobutane ring (5a–e). The structures of the final compounds were confirmed by elemental analyses, FT-IR, ¹H-NMR and ¹³C-NMR. The antioxidant and antitumor properties of the synthesized compounds were also investigated. Three of the triazole derivatives with p-tolyl, benzyl and phenyl substituents (5c–e) displayed good antioxidant and antitumor activity in comparison to the standards.     

Water Dynamics in Starch Based Confectionery Products including Different Types of Sugar

Starch-based confectionery products were prepared using different types of sugar. In addition to using different sugar, starch was replaced with soy protein isolate (SPI) in some of the products. ¹H NMR spin-lattice relaxation experiments were performed for the collection of products in a broad frequency range from 4 KHz to 30 MHz to get insight into the influence of different sugar types and SPI on the dynamics of water in composite gel systems. The relaxation data have been decomposed into relaxation contributions associated with two different pools of water molecules characterized by different mobility. The translation dynamics of water molecules has been quantitatively described in terms of a dedicated relaxation model. The influence of the sample composition (the type of sugar and/or the presence of SPI) on the water mobility was thoroughly discussed. The results indicate that the addition of soy protein does not affect water dynamics for samples including sucrose. In addition, as the complementary measurements, physical properties of the products, such as the moisture content, water activity and texture, were investigated in terms of X-ray diffraction and thermogravimetric analysis.     

Synthesis and spectroscopic properties of (N/O) mono- and dispirocyclotriphosphazene derivatives with benzyl pendant arms: study of biological activity

The Cl replacement reactions of hexachlorocyclotriphosphazene (trimer; N ₃ P ₃ Cl ₆ ) with sodium (N-benzyl)- aminopropanoxides (1 and 2) produced monospiro- (3 and 4), cis-, and trans-dispirocyclotriphosphazenes (13–16). The monospiro tetrakis-aminocyclotriphosphazenes (5–12) were obtained by the Cl substitutions of 3 and 4 with different secondary amines. The cis- (13 and 14) and trans-dispirophosphazenes (15 and 16) possessed 2 chiral P centers, and they were able to present meso and racemic forms, respectively. Moreover, the structures of compounds 5 and 14 were designated using X-ray data. The absolute configuration of compound 14 was found as SR in the solid state. Analytical and spectroscopic data of the phosphazenes were consistent with their suggested structures. Antimicrobial activities of the benzyl-pendant-armed cyclotriphosphazenes were scrutinized against G(+) and G(−) bacteria and yeast strains. The bacterium most affected by the synthesized compounds was Pseudomonas aeruginosa . Minimum inhibitory concentrations and minimal bacterial concentrations were in the range of 125–500 μM. Interactions between the phosphazenes (3–12 and 15) and plasmid DNA were studied with agarose gel electrophoresis. The phosphazene- DNA interaction studies of the cyclotriphosphazenes revealed that phosphazenes 3, 4, and 15 had a substantial effect on supercoiled DNA by cleavage of the double helix.     

Hydrothermally stable silica–alumina composite membranes for hydrogen separation

A thin layer (30–40 nm) of a dual-element silica–alumina composition was deposited on a porous alumina support by chemical vapor deposition (CVD) in an inert atmosphere at high temperature. Prior to CVD, an intermediate layer of γ-alumina was coated on the macroporous alumina support. The intermediate layer was prepared by the dip-coating and calcination of boehmite sols of different sizes to give a graded structure that was substantially free of defects. The resulting supported composite membrane had high permeance for hydrogen in the order of 2–3 × 10⁻⁷ mol m⁻² s⁻¹ Pa⁻¹ at 873 K with selectivities of H₂ over CH₄, CO and CO₂ of 940, 700 and 590, respectively. The membrane operated by a hopping mechanism involving jumps of permeating molecules between solubility sites. The presence of aluminum improved the hydrothermal stability of the membranes for periods in excess of 500 h at 873 K in 16% steam, allowing the permeance to remain above 10⁻⁷ mol m⁻² s⁻¹ Pa⁻¹, although with decreased selectivities.     

An exact solution procedure for multi-item two-echelon spare parts inventory control problem with batch ordering in the central warehouse

We consider a multi-item two-echelon inventory system in which the central warehouse operates under a (Q,R) policy, and the local warehouses implement basestock policy. An exact solution procedure is proposed to find the inventory control policy parameters that minimize the system-wide inventory holding and fixed ordering cost subject to an aggregate mean response time constraint at each facility.     

Physical and Covalent Immobilization of <Emphasis Type="Italic">Lipase</Emphasis> onto Amine Groups Bearing Thiol-Ene Photocured Coatings

In this study, amine groups containing thiol-ene photocurable coating material for lipase immobilization were prepared. Lipase (EC 3.1.1.3) from Candida rugosa was immobilized onto the photocured coatings by physical adsorption and glutaraldehyde-activated covalent bonding methods, respectively. The catalytic efficiency of the immobilized and free enzymes was determined for the hydrolysis of p-nitrophenyl palmitate and also for the synthesis of p-nitrophenyl linoleate. The storage stability and the reusability of the immobilized enzyme and the effect of temperature and pH on the catalytic activities were also investigated. The optimum pH for free lipase and physically immobilized lipase was determined as 7.0, while it was found as 7.5 for the covalent immobilization. After immobilization, the optimum temperature increased from 37 °C (free lipase) to 50–55 °C. In the end of 15 repeated cycles, covalently bounded enzyme retained 60 and 70 % of its initial activities for hydrolytic and synthetic assays, respectively. While the physically bounded enzyme retained only 56 % of its hydrolytic activity and 67 % of its synthetic activity in the same cycle period. In the case of hydrolysis V _max values slightly decreased after immobilization. For synthetic assay, the V _max value for the covalently immobilized lipase was found as same as free lipase while it decreased dramatically for the physically immobilized lipase. Physically immobilized enzyme was found to be superior over covalent bonding in terms of enzyme loading capacity and optimum temperature and exhibited comparable re-use values and storage stability. Thus, a fast, easy, and less laborious method for lipase immobilization was developed.