Structural Insights into the Interactions of Digoxin and Na+/K+-ATPase and Other Targets for the Inhibition of Cancer Cell Proliferation

Digoxin is a cardiac glycoside long used to treat congestive heart failure and found recently to show antitumor potential. The hydroxy groups connected at the C-12, C-14, and C-3′a positions; the C-17 unsaturated lactone unit; the conformation of the steroid core; and the C-3 saccharide moiety have been demonstrated as being important for digoxin’s cytotoxicity and interactions with Na⁺/K⁺-ATPase. The docking profiles for digoxin and several derivatives and Na⁺/K⁺-ATPase were investigated; an additional small Asn130 side pocket was revealed, which could be useful in the design of novel digoxin-like antitumor agents. In addition, the docking scores for digoxin and its derivatives were found to correlate with their cytotoxicity, indicating a potential use of these values in the prediction of the cancer cell cytotoxicity of other cardiac glycosides. Moreover, in these docking studies, digoxin was found to bind to FIH-1 and NF-κB but not HDAC, IAP, and PI3K, suggesting that this cardiac glycoside directly targets FIH-1, Na⁺/K⁺-ATPase, and NF-κB to mediate its antitumor potential. Differentially, digoxigenin, the aglycon of digoxin, binds to HDAC and PI3K, but not FIH-1, IAP, Na⁺/K⁺-ATPase, and NF-κB, indicating that this compound may target tumor autophagy and metabolism to mediate its antitumor propensity.     

Isoflavonoid-Antibiotic Thin Films Fabricated by MAPLE with Improved Resistance to Microbial Colonization

Staphylococcus aureus (Gram-positive) and Pseudomonas aeruginosa (Gram-negative) bacteria represent major infectious threats in the hospital environment due to their wide distribution, opportunistic behavior, and increasing antibiotic resistance. This study reports on the deposition of polyvinylpyrrolidone/antibiotic/isoflavonoid thin films by the matrix-assisted pulsed laser evaporation (MAPLE) method as anti-adhesion barrier coatings, on biomedical surfaces for improved resistance to microbial colonization. The thin films were characterized by Fourier transform infrared spectroscopy, infrared microscopy, and scanning electron microscopy. In vitro biological assay tests were performed to evaluate the influence of the thin films on the development of biofilms formed by Gram-positive and Gram-negative bacterial strains. In vitro biocompatibility tests were assessed on human endothelial cells examined for up to five days of incubation, via qualitative and quantitative methods. The results of this study revealed that the laser-fabricated coatings are biocompatible and resistant to microbial colonization and biofilm formation, making them successful candidates for biomedical devices and contact surfaces that would otherwise be amenable to contact transmission.     

Stoichiometric and Catalytic Inter‐ and Intramolecular Hydroamination of Terminal Alkynes by Frustrated Lewis Pairs

Frustrated Lewis pairs (FLPs) based on sterically encumbered anilines and the Lewis acid B(C₆F₅)₃ were found to react with terminal alkynes effecting intermolecular hydroamination affording iminium alkynylborate species of the form [RPhN?C(R′)Me][R′CCB(C₆F₅)₃]. In these cases, the reagent ratio of borane, aniline, and alkyne is 1:1:2. These reactions could also be performed in an intramolecular fashion by using anilines with alkynyl substituents effecting cyclization reactions. The use of 10 mol % B(C₆F₅)₃ under a H₂ atmosphere provides a one‐pot synthesis of the pyrrolidine 12 , the piperidines 13 – 15 , the azepane 16 , the isoindoline 17 , and the benzoxazine 18 .     

Thermal Analysis of Micro- and Nano-Lignocellulosic Reinforced Styrene Maleic Anhydride Composite Foams

The aim of this study was to measure the thermal properties of foamed nano/macro filler–reinforced styrene maleic anhydride (SMA) composites. SMA (66%) as a polymer matrix (10% maleic anhydride content) and various fillers including wood flour, starch, α-cellulose, microcrystalline cellulose and cellulose nanofibrils as reinforcing agents (30%) and lubricant (4%) were used to manufacture the composites in a twin-screw extruder. According to the thermogravimetric analysis (TGA) results, thermal degradation of all the foamed composites was found to be lower than that of SMA composites. The storage modulus values were negatively affected with a second time foaming (reprocessing [recycling] the initially processed composites a second time), as were loss modulus and T_g. As a result, second-time-foamed composite modulus values were lower than those of the foamed composites. According to the melt flow index (MFI) results, viscosity of the SMA was found to increase with the addition of fillers.     

Acceleration of Acetal Hydrolysis by Remote Alkoxy Groups: Evidence for Electrostatic Effects on the Formation of Oxocarbenium Ions

In contrast to observations with carbohydrates, experiments with 4‐alkoxy‐substituted acetals indicate that an alkoxy group can accelerate acetal hydrolysis by up to 20‐fold compared to substrates without an alkoxy group. The acceleration of ionization in more flexible acetals can be up to 200‐fold when compensated for inductive effects.     

High Ethene/Ethane Selectivity in 2,2′‐Bipyridine‐Based Silver(I) Complexes by Removal of Coordinated Solvent

Following removal of coordinated CH₃CN, the resulting complexes [Ag^I(2,2′‐bipyridine)][BF₄] ( 1 ) and [Ag^I(6,6′‐dimethyl‐2,2′‐bipyridine)][OTf] ( 2 ) show ethene/ethane sorption selectivities of 390 and 340, respectively, and corresponding ethene sorption capacities of 2.38 and 2.18 mmol g^?1 when tested at an applied gas pressure of 90 kPa and a temperature of (20±1) °C. These ethene/ethane selectivities are 13 times higher than those reported for known solid sorbents for ethene/ethane separation. For 2 , ethene sorption reached 90 % of equilibrium capacity within 15 minutes, and this equilibrium capacity was maintained over the three sorption/desorption cycles tested. The rates of ethene sorption were also measured. To our knowledge, these are the first complexes, designed for olefin/paraffin separations, which have open silver(I) sites. The high selectivities arise from these open silver(I) sites and the relatively low molecular surface areas of the complexes.     

Facile Protocol for Catalytic Frustrated Lewis Pair Hydrogenation and Reductive Deoxygenation of Ketones and Aldehydes

A series of ketones and aldehydes are reduced in toluene under H₂ in the presence of 5 mol % B(C₆F₅)₃ and either cyclodextrin or molecular sieves affording a facile metal‐free protocol for reduction to alcohols. Similar treatment of aryl ketones resulted in metal‐free deoxygenation yielding aromatic hydrocarbons.