Synthesis and biological evaluation of Oblongifolin C derivatives as c-Met inhibitors

Oblongifolin C, one of the polyprenylated benzoylphloroglucinol natural products (PPAPs) isolated from the fruits of Garcinia yunnanensis Hu, was recently discovered to be a potent anti-tumor agent. A collection of 12 derivatives with modifications on the benzophenone moieties were synthesized and tested for c-Met kinase inhibition and cytotoxicity against the HepG2, Miapaca-2, HCC827, Hela, A549, AGS, and HT-29 cell lines in vitro. An oxidized derivative, 10, was found to possess strong inhibition and anti-migration properties in the HCC827 cell line and serves as a potential lead compound for the development of new anticancer drugs. In addition, structure–activity relationships (SAR) were also evaluated to provide key information for future anticancer drug development.     

Design,synthesis, and structure–activity relationship of novel and effective apixaban derivatives as FXa inhibitors containing 1,2,4-triazole/pyrrole derivatives as P2 binding element

Four series of novel and potent FXa inhibitors possessing the 1,2,4-triazole moiety and pyrrole moiety as P2 binding element and dihydroimidazole/tetrahydropyrimidine groups as P4 binding element were designed, synthesized, and evaluated for their anticoagulant activity in human and rabbit plasma in vitro. Most compounds showed moderate to excellent activity. Compounds 14a, 16, 18c, 26c, 35a, and 35b were further examined for their inhibition activity against human FXa in vitro and rat venous thrombosis in vivo. The most promising compound 14a, with an IC₅₀ (FXa) value of 0.15 μM and 99% inhibition rate, was identified for further evaluation as an FXa inhibitor.     

Utilizing Environmental Friendly Iron as a Substitution Element in Spinel Structured Cathode Materials for Safer High Energy Lithium‐Ion Batteries

Suppressing oxygen release from lithium ion battery cathodes during heating is a critical issue for the improvement of the battery safety characteristics because oxygen can exothermically react with the flammable electrolyte and cause thermal runaway. Previous studies have shown that oxygen release can be reduced by the migration of transition metal cations from octahedral sites to tetrahedral sites during heating. Such site‐preferred migration is determined by the electronic structure of cations. Taking advantage of the unique electronic structure of the environmental friendly Fe, this is selected as substitution element in a high energy density material LiNi_0.5Mn_1.5O₄ to improve the thermal stability. The optimized LiNi_0.33Mn_1.33Fe_0.33O₄ material shows significantly improved thermal stability compared with the unsubstituted one, demonstrated by no observed oxygen release at temperatures as high as 500°C. Due to the electrochemical contribution of Fe, the high energy density feature of LiNi_0.5Mn_1.5O₄ is well preserved.     

KCTD5 is endowed with large,functionally relevant,interdomain motions

The KCTD family is an emerging class of proteins that are involved in important biological processes whose biochemical and structural properties are rather poorly characterized or even completely undefined. We here used KCTD5, the only member of the family with a known three-dimensional structure, to gain insights into the intrinsic structural stability of the C-terminal domain (CTD) and into the mutual dynamic interplay between the two domains of the protein. Molecular dynamics (MD) simulations indicate that in the simulation timescale (120 ns), the pentameric assembly of the CTD is endowed with a significant intrinsic stability. Moreover, MD analyses also led to the identification of exposed β-strand residues. Being these regions intrinsically sticky, they could be involved in the substrate recognition. More importantly, simulations conducted on the full-length protein provide interesting information of the relative motions between the BTB domain and the CTD of the protein. Indeed, the dissection of the overall motion of the protein is indicative of a large interdomain twisting associated with limited bending movements. Notably, MD data indicate that the entire interdomain motion is pivoted by a single residue (Ser150) of the hinge region that connects the domains. The functional relevance of these motions was evaluated in the context of the functional macromolecular machinery in which KCTD5 is involved. This analysis indicates that the interdomain twisting motion here characterized may be important for the correct positioning of the substrate to be ubiquitinated with respect to the other factors of the ubiquitination machinery.     

Effect of water stress on germination of some Hungarian wheat landraces varieties

In order to examine germination characters, seedling parameters, water relative content, tolerance index and enzyme activities of seven Hungarian wheat landraces varieties (Tiszadadai, Riscsei, Komloi, Leweucei, Mateteleki, Mikebudai and Nyiradi) under five concentrations of water stress (0, 6, 12, 18, and 24%) of polyethylene glycol (PEG-6000). A laboratory experiment has been conducted through Factorial Experiment in Randomized Complete Block Design (RCBD) with four repetitions at Research Institute of Nyiregyhaza, Hungary. From the obtained results, Leweucei variety was surpassed other studied verities under study and recorded the highest values of all studied characters followed by Mateteleki, Komloi, Nyiradi, Riscsei, Tiszadadai and Mikebudai. Increasing water stress (PEG-6000) from 0 to 6, 12, 18 and 24% significantly reduced germination characters, seedlings parameters, water relative content (WRC), tolerance index and α and β-amylases activities. Generally, under water stress condition, Leweucei and Mateteleki varieties were recorded the highest values of water relative content (WRC), tolerance index (TI) and α and β-amylases activities as well as able to prompt better drought tolerance and could be suggested as a good resource for breeding programs and cultivation under drought stress conditions compared with other wheat landraces varieties.     

Synthesis and photoluminescence properties of co‐polyamides with anthrazoline‐containing units in the main chain

A series of anthrazoline‐containing monomers are synthesized, and eight co‐polyamides of different chemical structures, containing 1,9‐anthrazoline fragments in the main chain, are obtained and investigated. Photoluminescent, stress–strain, and thermal properties of these polymers are studied. It is shown that polymers with fragments of 4,4′‐(pyrido[3,2‐g]‐quinoline‐2,8‐diyl)dianiline and 4,4′‐(10‐methylpyrido[3,2‐g]quinoline‐2,8‐diyl)dianiline possess an intense luminescence in the range 550–650 nm. The performed investigations made it possible to determine the effect of substituents of various natures in the anthrazoline cycle and the position of amide group (meta‐ and para‐configurations) on optical, stress‐strain, and thermal properties of copolymers, opening up a prospect for further developments of principles of design of polymers with optimal characteristics.     

Responses of radish (Raphanus sativus) to drought stress

With this study the effects of water deficit on radish growth, dry mass production and partitioning, source–sink relations, physiological responses and accumulation of secondary metabolites in storage roots and leaves have been investigated. Three water stress treatments were applied: (Control) 100% of water holding capacity (WHC), (WS50) 50% of WHC, (WS30) 30% of WHC. Water stress was effectively acquired starting from 287 growing degree days (GDD) as demonstrated by the lower values of relative water content (RWC), higher leaf temperature and NIR‐based water indices values in water stressed conditions. Water stress reduced storage root dry weight by 27% at WS50 and 53% at WS30 as well as leaf dry matter accumulation (by 23% and 31% in WS50 and WS30, respectively), expansion (by 28% and 45% in WS50 and WS30, respectively) and specific leaf area (by 7% and 20% in WS50 and WS30, respectively) at 403 GDD. The increasing of leaf‐to‐root mass (L/R) and leaf area‐to‐root mass (LA/R) ratios indicated less dry matter allocation into storage organs under water stress conditions. Besides, water shortage increased leaf greenness as estimated by the higher soil–plant analysis development (SPAD) values (+14% and +20% on average for WS50 and WS30, respectively); other reflectance indices only partially confirmed SPAD readings. Substantially, water limitation did not significantly influence total anthocyanin content, ABTS‐radical scavenging activity and total free phenolic compounds in storage roots, as well as the total free phenolic compounds in leaves. Radish showed a strong plasticity in its adaptation to drought thanks to avoidance mechanisms such as constrained leaf development, increased leaf thickness and adjusted source–sink relationships.