Aminopyridyl/Pyrazinyl Spiro[indoline-3,4′-piperidine]-2-ones As Highly Selective and Efficacious c‑Met/ALK Inhibitors

A series of novel aminopyridyl/pyrazinyl-substituted spiro­[indoline-3,4′-piperidine]-2-ones were designed, synthesized, and tested in various in vitro/in vivo pharmacological and antitumor assays. 6-[6-Amino-5-[(1<i>R</i>)-1-(2,6-dichloro-3-fluorophenyl)­ethoxy]-3-pyridyl]-1′-methylspiro­[indoline-3,4′-piperidine]-2-one (compound <b>5b</b> or <b>SMU-B</b>) was identified as a potent, highly selective, well-tolerated, and orally efficacious c-Met/ALK dual inhibitor, which showed pharmacodynamics effect by inhibiting c-Met phosphorylation in vivo and significant tumor growth inhibitions (>50%) in GTL-16 human gastric carcinoma xenograft models

Construction of a Tannase-Immobilized Magnetic Graphene Oxide/Polymer Nanobiocatalyst with Enhanced Enzyme Stability for High-Efficiency Transformation of Tannins

Highly efficient biotransformation of natural compounds into sustainable biochemical products has attracted great attention. The integration of nanoscience and biotechnology provides attractive solutions for this purpose. Herein, we report the fabrication of a nanobiocatalyst employing a magnetic graphene oxide/polymer nanocomposite as a robust carrier for immobilizing the tannase enzyme, which catalyzes the bioconversion of tannin into gallic acid and glucose. Attributed to the covalent immobilization and propitious interface properties of the coated polymers comprising polyethylenimine and sodium hyaluronate, the nanobiocatalyst is stable without compromising the enzymatic activity. The nanobiocatalyst exhibits 91.8% activity of original tannase and a high enzyme bound amount of 356.8 mg g–1. The stability tests at variable temperatures (30–80 °C) and under pH conditions (4.0–9.0), various inhibitors, and a long-term storage process (25 days) reveal that the heterofunctional support and surface microenvironment facilitate better stability, adaptability, and tolerance ability of the nanobiocatalyst modified with a multicomponent polymer in comparison to the free enzyme and the nanobiocatalyst modified with the monocomponent polyethylenimine. The nanobiocatalyst maintains 94.2% of its initial activity after 10 consecutive uses and is 100% recoverable by applying an external magnet. Moreover, the nanobiocatalyst is used to hydrolyze 96.5 and 95.1% tannins in extracts from Chinese Torreya grandis testa and cake, respectively. These results establish the practicability of magnetic graphene oxide-based supports for immobilizing tannase and the promising application of immobilized tannase for efficient tannin hydrolysis

Magnetic-Encoded Fluorescent Multifunctional Nanospheres for Simultaneous Multicomponent Analysis

In this study, magnetic-encoded fluorescent (CdTe/Fe₃O₄)@SiO₂ multifunctional nanospheres were constructed by adjusting the initial concentration of Fe₃O₄ in a fabrication process based on reverse microemulsion. The resultant multifunctional nanospheres were characterized by transmission electron microscopy, X-ray diffraction measurements, fluorescence spectrophotometry, and vibrating sample magnetometry. They showed good fluorescence properties, gradient magnetic susceptibility (weak, moderate, and strong), and easy biofunctionalization for biomolecules, such as immunoglobulin G (IgG), protein, and antibody. Then the capture efficiency of the (CdTe/Fe₃O₄)@SiO₂ nanospheres were investigated by using the fluorophore-labeled IgG-conjugated nanospheres as a model. Further studies demonstrated the ability of these (CdTe/Fe₃O₄)@SiO₂ multifunctional nanospheres to accomplish sequentially magnetic separation, capture, and fluorescent detection for each corresponding antigen of CA125, AFP, and CEA with a detection limit of 20 KU/L, 10 ng/mL, and 5 ng/mL, respectively, from a mixed sample under a certain external magnetic field within a few minutes. The strategy of combining magnetic-encoding-based separation and fluorescence-based detection proposed in this study shows great potential to achieve easy, rapid, economical, and near-simultaneous multicomponent separation and analysis for a variety of targets such as drugs, biomarkers, pathogens, and so on