2′-Fucosyllactose Suppresses Angiogenesis and Alleviates Toxic Effects of 5-Fu in a HCT116 Colon Tumor-Bearing Model

The present study was aimed at examining the anti-tumor effects and molecular mechanisms of 2′-fucosyllactose (2′-FL). At the beginning, the viabilities of four types of colon cancer cells were analyzed after exposure to increasing concentrations of 2′-FL, and HCT116 cells were selected as the sensitive ones, which were applied in the further experiments; then, interestingly, 2′-FL (102.35 µM) was found to induce apoptosis of HCT116 cells, which coincides with significant changes in VEGFA/VEGFR2/p-PI3K/p-Akt/cleaved Caspase3 proteins. Next, in a tumor-bearing nude mouse model, HCT116 was chosen as the sensitive cell line, and 5-fluorouracil (5-Fu) was chosen as the positive medicine. It was noteworthy that both 2′-FL group (2.41 ± 0.57 g) and 2′FL/5-Fu group (1.22 ± 0.35 g) had a significantly lower tumor weight compared with the control (3.87 ± 0.79 g), suggesting 2′-FL could inhibit colon cancer. Since 2′-FL reduced the number of new blood vessels and the malignancy of tumors, we confirmed that 2′-FL effectively inhibited HCT116 tumors, and its mechanism was achieved by regulating the VEGFA/VEGFR2/PI3K/Akt/Caspase3 pathway. Moreover, though HE staining and organ index measurement, 2′-FL was validated to alleviate toxic effects on liver and kidney tissue when combining with 5-Fu. In conclusion, 2′-FL had certain anti-tumor and detoxification effects.     

Push-Pull Structures Based on 2-Aryl/thienyl Substituted Quinazolin-4(3H)-ones and 4-Cyanoquinazolines

Design and synthesis of 2-(aryl/thiophen-2-yl)quinazolin-4(3H)-ones and 4-cyano-2-arylquinazolines with Et₂N-, Ph₂N- or carbazol-9-yl- electron donating fragment are described. The key photophysical properties of these compounds have been studied by UV/Vis absorption and fluorescence spectroscopy in solvents of different polarity (toluene and MeCN). 2-(Aryl/thiophen-2-yl)quinazolin-4(3H)-ones show fluorescence in blue-green region in toluene solution with quantum yields up to 89% in the case of 2-(4’-N,N-diphenylamino[1,1’-biphenyl]-4-yl)-quinazolin-4(3H)-one. Moreover, triphenylamino derivative based on quinazolin-4(3H)-one with para-phenylene linker displays the highest quantum yield of 40% in powder. The fluorescence QY of Et₂N and Ph₂N derivatives decrease when going from toluene to MeCN solution, whereas carbazol-9-yl counterparts demonstrate strengthening of intensity that emphasizes the strong influence of donor fragment nature on photophysical properties. 4-Cyanoquinazolines are less emissive in both solvents, as well as, in solid state. The introduction of cyano group into position 4 leads to orange/red colored powder and dual emission bands. Some molecules demonstrate the increase in emission intensity upon addition of water to MeCN solution. According to frontier molecular orbitals (HOMO, LUMO) calculations, the energy gap of 4-cyanoquinazoline decreases by more than 1 eV compared to quinazolin-4-one, that is consistent with experimental data.     

An Overview on the Synthesis of Fused Pyridocoumarins with Biological Interest

Pyridocoumarins are a class of synthetic and naturally occurring organic compounds with interesting biological activities. This review focuses on the synthetic strategies for the synthesis of pyridocoumarins and presents the biological properties of those compounds. The synthesis involves the formation of the pyridine ring, at first, from a coumarin derivative, such as aminocoumarins, hydroxycoumarins, or other coumarins. The formation of a pyranone moiety follows from an existing pyridine or piperidine or phenol derivative. For the above syntheses, [4 + 2] cycloaddition reactions, multi-component reactions (MCR), as well as metal-catalyzed reactions, are useful. Pyridocoumarins present anti-cancer, anti-HIV, antimalarial, analgesic, antidiabetic, antibacterial, antifungal, anti-inflammatory, and antioxidant activities.     

New Pyrimidine-5-Carbonitriles as COX-2 Inhibitors: Design,Synthesis, Anticancer Screening,Molecular Docking,and In Silico ADME Profile Studies

Two series of cyanopyrimidine hybrids were synthesized bearing either benzo[d]imidazole, benzo[d]oxazole, benzo[d]thiazole, and benzo[b]thiophene derivatives via methylene amino linker 3a–3d (Formula A) or various sulphonamide phenyl moieties 5a–5d (Formula B) at the C-2 position. All compounds’ cyclooxygenase COX-2 inhibitory activities were evaluated, and all synthesized compounds demonstrated potent activity at minimal concentrations, with IC₅₀ values in the submicromolar range. Compounds 3b, 5b, and 5d were discovered to be the most active pyrimidine derivatives, with the highest COX-2 percent inhibition and IC₅₀ values being nearly equal to Celecoxib and approximately 4.7-, 9.3-, and 10.5-fold higher than Nimesulide. Furthermore, the pyrimidine derivatives 3b, 5b, and 5d demonstrated anticancer activity comparable to or better than doxorubicin against four cell lines, i.e., MCF-7, A549, A498, and HepG2, with IC₅₀ values in nanomolar in addition to low cytotoxicity on the normal W38-I cell line. The effect of compound 5d on cell cycle progression and apoptosis induction was investigated, and it was found that compound 5d could seize cell growth at the sub-G1 and G2/M phases, as well as increase the proportion of early and late apoptotic rates in MCF-7 cells by nearly 13- and 60-fold, respectively. Moreover, in silico studies for compounds 3b, 5b, and 5d revealed promising findings, such as strong GIT absorption, absence of BBB permeability, nil-to-low drug–drug interactions, good oral bioavailability, and optimal physicochemical properties, indicating their potential as promising therapeutic candidates.     

One-Step Calcination to Gain Exfoliated g-C3N4/MoO2 Composites for High-Performance Photocatalytic Hydrogen Evolution

The difficulty of exposing active sites and easy recombination of photogenerated carriers have always been two critical problems restricting the photocatalytic activity of g-C₃N₄. Herein, a simple (NH₄)₂MoO₄-induced one-step calcination method was successfully introduced to transform bulk g-C₃N₄ into g-C₃N₄/MoO₂ composites with a large specific surface area. During the calcination, with the assistance of NH₃ and water vapor produced by ammonium molybdate, the pyrolytical oxidation and depolymerization of a g-C₃N₄ interlayer were accelerated, finally realizing the exfoliation of the g-C₃N₄. Furthermore, another pyrolytical product of ammonium molybdate was transformed into MoO₂ under an NH₃ atmosphere, which was in situ loaded on the surface of a g-C₃N₄ nanosheet. Additionally, the results of photocatalytic hydrogen evolution under visible light show that the optimal g-C₃N₄/MoO₂ composite has a high specific surface area and much improved performance, which is 4.1 times that of pure bulk g-C₃N₄. Such performance improvement can be attributed to the full exposure of active sites and the formation of abundant heterojunctions. However, with an increasing feed amount of ammonium molybdate, the oxidation degree of g-C₃N₄ was enhanced, which would widen the band gap of g-C₃N₄, leading to a weaker response ability to visible light. The present strategy will provide a new idea for the simple realization of exfoliation and constructing a heterojunction for g-C₃N₄ simultaneously.     

Synthesis of 2-Aminopyrimidine Derivatives and Their Evaluation as β-Glucuronidase Inhibitors: In Vitro and In Silico Studies

Currently the discovery and development of potent β-glucuronidase inhibitors is an active area of research due to the observation that increased activity of this enzyme is associated with many pathological conditions, such as colon cancer, renal diseases, and infections of the urinary tract. In this study, twenty-seven 2-aminopyrimidine derivatives 1–27 were synthesized by fusion of 2-amino-4,6-dichloropyrimidine with a variety of amines in the presence of triethylamine without using any solvent and catalyst, in good to excellent yields. All synthesized compounds were characterized by EI-MS, HREI-MS and NMR spectroscopy. Compounds 1–27 were then evaluated for their β-glucuronidase inhibitory activity, and among them, compound 24 (IC₅₀ = 2.8 ± 0.10 µM) showed an activity much superior to standard D-saccharic acid 1,4-lactone (IC₅₀ = 45.75 ± 2.16 µM). To predict the binding mode of the substrate and β-glucuronidase, in silico study was performed. Conclusively, this study has identified a potent β-glucuronidase inhibitor that deserves to be further studied for the development of pharmaceutical products.     

A Modified Vancomycin Molecule Confers Potent Inhibitory Efficacy against Resistant Bacteria Mediated by Metallo-β-Lactamases

Multidrug-resistant bacterial infections mediated by metallo-β-lactamases (MβLs) have grown into an emergent health threat, and development of novel antimicrobials is an ideal strategy to combat the infections. Herein, a novel vancomycin derivative V_b was constructed by conjugation of triazolylthioacetamide and vancomycin molecules, characterized by reverse-phase high performance liquid chromatography (HPLC) and confirmed by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS). The biological assays revealed that V_b effectively inhibited S. aureus and methicillin-resistant S. aureus (MRSA), gradually increased the antimicrobial effect of β-lactam antibiotics (cefazolin, meropenem and penicillin G) and exhibited a dose-dependent synergistic antibacterial effect against eight resistant strains tested, which was confirmed by the time-kill curves determination. Most importantly, V_b increased the antimicrobial effect of meropenem against the clinical isolates EC08 and EC10 and E. coli producing ImiS and CcrA, resulting in a 4- and 8-fold reduction in MIC values, respectively, at a dose up to 32 μg/mL. This work offers a promising scaffold for the development of MβLs inhibitors, specifically antimicrobials for clinically drug-resistant isolates.     

Discovery of New Glucose Uptake Inhibitors as Potential Anticancer Agents by Non-Radioactive Cell-Based Assays

Tumor cells rely on aerobic glycolysis to support growth and survival, thus require more glucose supply. Glucose transporters GLUTs, primarily GLUT1, are overexpressed in various cancers. Targeting GLUTs has been regarded as a promising anticancer strategy. In this study, we first evaluated 75 potential GLUT1 inhibitors obtained from virtual screening of the NCI chemical library by a high-throughput cell-based method using a fluorescent glucose analogue 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxy-d-glucose (2-NBDG) in COS-7 and SKOV3 cells that express high levels of GLUT1. Four compounds, #12, #16, #43 and #69, that significantly inhibited glucose uptake were further evaluated using flow cytometry directly measuring 2-NBDG uptake at the single-cell level and a Glucose Uptake-Glo^TM assay indirectly measuring 2-deoxy-d-glucose uptake in SKOV3, COS-7 or MCF-7 cells. The inhibitory effect on cancer cell growth was also determined in SKOV3 and MCF-7 cells, and #12 exhibited the best growth inhibitory effect equivalent to a known GLUT1 inhibitor WZB117. Although the anticancer effect of the identified potential GLUT1 inhibitors was moderate, they may enhance the activity of other anticancer drugs. Indeed, we found that #12 synergistically enhanced the anticancer activity of metformin in SKOV3 ovarian cancer cells.     

Ultrathin Two-Dimensional Fe–Co Bimetallic Oxide Nanosheets for Separator Modification of Lithium–Sulfur Batteries

The shuttle effect is understood to be the most significant issue that needs to be solved to improve the performance of lithium–sulfur batteries. In this study, ultrathin two-dimensional Fe–Co bimetallic oxide nanosheets were prepared using graphene as a template, which could rapidly catalyze the conversion of polysulfides and inhibit the shuttle effect. Additionally, such ultrathin nanostructures based on graphene provided sufficient active sites and fast diffusion pathways for lithium ions. Taking into account the aforementioned benefits, the ultrathin two-dimensional Fe–Co bimetallic oxide nanosheets modified separator assembled lithium–sulfur batteries delivered an incredible capacity of 1044.2 mAh g⁻¹ at 1 C and retained an excellent reversible capacity of 859.4 mAh g⁻¹ after 100 cycles. Even under high loading, it still achieved high area capacity and good cycle stability (92.6% capacity retention).     

Photoelectron Properties and Organic Molecules Photodegradation Activity of Titania Nanotubes with CuxO Nanoparticles Heat Treated in Air and Argon

Titania is very famous photocatalyst for decomposition of organic pollutants. Its photocatalytic properties significantly depend on the morphology and chemical composition of the samples. Herein, the TiO₂ nanotubes/Cu_xO nanoheterostructures have been synthesized and the effect of heat treatment performed in molecular atmospheres of air and argon on their photoelectrochemical and photocatalytic properties has been studied. The prepared samples have a higher reaction rate constant compared to TiO₂ nanotubes in the decomposition reaction of methylene blue molecules. It is established that in argon treated nanoheterostructures, the copper oxide is present in two phases, CuO and Cu₂O, while in air treated ones there is only CuO. In the TiO₂ nanotubes/Cu_xO samples, Cu²⁺ ions and molecular O₂⁻ radicals were detected while in TiO₂ nanotubes only carbon dangling bond defects are present. The dynamics of O₂⁻ radicals under illumination are discussed. It was shown that the TiO₂ nanotubes do not exhibit photocatalytic activity under visible light. The mechanism of the photocatalytic reaction on the surface of the TiO₂ nanotubes/Cu_xO samples was proposed. It is assumed that a photocatalytic decomposition of organic molecules under visible light at the surface of the nanoheterostructures under investigation is realized mainly by the reaction of these molecules with photogenerated O₂⁻ radicals. The results obtained are completely original and indicate the high promise of the prepared photocatalysts.