Molecules最新文献

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by extensive neurodegeneration and consequent severe memory loss. Apolipoprotein E4 (ApoE4) is the strongest genetic risk factor for AD, with its pathological effects linked to structural instability and altered interactions with lipids and other important disease proteins including amyloid beta (Aβ) and tau (τ). Therefore, correcting and stabilizing the ApoE4 structure has emerged as a promising therapeutic strategy for mitigating its detrimental effects. In this study, we investigated naturally occurring bioavailable flavonoids as ApoE4 stabilizers, focusing on their potential to modulate ApoE4 structure and function. A comprehensive investigation of a focused database using our integrated computational and experimental screening protocol led to the identification of Isobavachin as a potential corrector and stabilizer of ApoE4 structure. In addition, a few other bioavailable flavonoids with similar stabilizing properties were identified, albeit to a much lesser extent as compared to Isobavachin. The findings support the therapeutic potential of flavonoids as ApoE4 modulators and highlight Isobavachin as a lead candidate for further preclinical evaluation. These results provide new insights into the pharmacological targeting of ApoE4 and open avenues for the development of flavonoid-based, ApoE-directed therapies for AD.

The hazardousness of solvents used in synthetic organic chemistry is well established. In this context, it is relevant to search for safer and greener alternatives. Within the last decades, deep eutectic solvents have been considered as possible and promising alternatives. Consequently, this study aims at using deep eutectic solvents to synthesize an emerging class of heteroaromatic compounds named thiazolo[5,4-d]thiazoles, for which interest is growing in the field of organics, electronics, and biology. To address this challenge, we developed a straightforward synthetic protocol consisting of condensing dithiooxamide and aromatic aldehyde in deep eutectic solvents to yield the desired thiazolo[5,4-d]thiazole without further purification. The first hit was obtained with the well-known L-proline:glycerol (1:2) mixture at 130 °C. However, dithiooxamide is degraded under these conditions, leading to the formation of impurities that may arise from the consequent amount of reactive L-proline. Reaction conditions were optimized by modifying the deep eutectic solvent nature and proportions, applying various temperatures, changing the activation and heating source, or adding auxiliary oxidants. As a consequence, eight thiazolo[5,4-d]thiazoles were synthesized in equal or better yields (20 to 75%) than the reported procedure under safe and eco-friendly conditions in a mixture of L-proline and ethylene glycol (1:50) with sodium metabisulfite at 130 °C for one hour.

Numerous studies have previously demonstrated the antimicrobial activity of plant extracts rich in procyanidins. However, these investigations that focused on uncharacterized extracts do not provide information on the structure-activity relationships of these compounds. The aim of this work was to investigate the antibacterial and antibiofilm properties of 27 phenolics with coumarin, naphthoquinone and pyranone moieties against foodborne microorganisms, as well as to establish structure-activity relationships. Minimal inhibitory concentrations (MICs) for each compound were investigated, as well as their ability for inhibiting biofilm formation as well as disrupting previously formed biofilms by food pathogens. Our compounds show high antibacterial and antibiofilm activities against Gram-positive bacteria. Regarding the structure-activity relationships observed, the coumarin moiety seems to favor the antibacterial activity against both S. aureus strains assayed, while a naphthoquinone moiety enhances antibacterial effects against B. cereus. Moreover, the replacement of OH groups in the B-ring by methoxy groups impairs antibacterial activity of the compounds against target bacteria, while the presence of Cl or OH groups in the molecules seems to enhance the inhibition of biofilm formation as well as the disruption of preformed biofilms. These results may be of great relevance for the food sector, increasing the options of additives that can be used industrially.

This work explores the self-assembly and optical properties of a novel chiral, aromatic-rich Boc-Phe-Phe dipeptide derivative functionalized with a benzothiazole bicyclic ring that forms supramolecular structures. Leveraging the well-known self-assembling capabilities of diphenylalanine dipeptides, this modified derivative introduces a heterocyclic benzothiazole unit that significantly enhances the fluorescence of the resulting nanostructures. The derivative's rich aromatic character drives the formation of supramolecular structures through self-organization mechanisms influenced by quantum confinement. By adjusting the solvent system, the nanostructures exhibit tunable morphologies, ranging from nanospheres to nanobelts. The nonlinear optical properties of these self-assembled structures were studied and an estimated deff of ~0.9 pm/V was obtained, which is comparable to that reported for the highly aromatic triphenylalanine peptide.

The electrocatalytic reduction of CO₂ (ECO₂RR) to syngas with tunable CO/H₂ ratios offers a promising route for sustainable energy conversion and chemical production. Here, we report a series of N-doped carbon black (NCBx) catalysts with tailored nitrogen species that enable precise control over the composition of syngas. Among the catalysts, NCB3 exhibits the optimal performance, achieving high CO selectivity (64.14%) and activity (1.9 mA cm^-2) in an H-type cell at -0.9 V. Furthermore, NCB3 produces syngas with a wide range of CO/H₂ ratios (0.52 to 4.77) across the applied potentials (-0.5 to -1.0 V). Stability tests confirm the robust durability of NCB3, which maintains consistent activity and selectivity over prolonged electrolysis. This work demonstrates the critical role of nitrogen species in tuning ECO₂RR pathways and establishes a strategy for designing efficient and stable carbon-based catalysts for CO₂ utilization and syngas production.

Nasturtium officinale R. Br. (watercress) is an endangered species with valuable pharmaceutical, cosmetic, and nutritional properties. The purpose of this work was to evaluate the phytochemical profile and biological activity of extracts from microshoot cultures grown in PlantForm bioreactors and the parent plant material. After 20 days of cultivation, the cultures achieved the best results both in terms of key active ingredient content and biological activity. The glucosinolates (GSL) profile by the UHPLC-DAD-MS/MS method showed that the dominant compounds were glucobrassicin (493.00 mg/100 g DW, 10 days) and gluconasturtiin (268.04 mg/100 g DW, 20 days). The highest total polyphenol content (TPC) was obtained after a 20-day growth period (2690 mg GAE/100 g DW). Among polyphenols, the dominant compounds in the extracts from in vitro cultures were sinapinic acid (114.83 mg/100 g DW, 10 days) and ferulic acid (87.78 mg/100 g DW, 20 days). The highest antioxidant potential assessed by ABTS and DPPH assays was observed for ethanol extracts. The best results for inhibiting hyperpigmentation (18.12%) were obtained for ethanol extracts and anti-elastase activity (79.78%) for aqueous extract from N. officinale microshoot cultures. The extracts from microshoot cultures inhibited the growth of bacteria, including Cutibacterium acnes (MIC = 0.625 mg/mL). Antioxidant tests and the chelating capacity of iron ions Fe²⁺ of the face emulsion with N. officinale extracts showed higher results than the control.

Enzyme immobilization plays a critical role in enhancing the efficiency and sustainability of biocatalysis, addressing key challenges such as limited enzyme stability, short shelf life, and difficulties in recovery and recycling, which are pivotal for green chemistry and industrial applications. Classical approaches, including adsorption, entrapment, encapsulation, and covalent bonding, as well as advanced site-specific methods that integrate enzyme engineering and bio-orthogonal chemistry, were discussed. These techniques enable precise control over enzyme orientation and interaction with carriers, optimizing catalytic activity and reusability. Key findings highlight the impact of immobilization on improving enzyme performance under various operational conditions and its role in reducing process costs through enhanced stability and recyclability. The review presents numerous practical applications of immobilized enzymes, including their use in the pharmaceutical industry for drug synthesis, in the food sector for dairy processing, and in environmental biotechnology for wastewater treatment and dye degradation. Despite the significant advantages, challenges such as activity loss due to conformational changes and mass transfer limitations remain, necessitating tailored immobilization protocols for specific applications. The integration of immobilization with modern biotechnological advancements, such as site-directed mutagenesis and recombinant DNA technology, offers a promising pathway for developing robust, efficient, and sustainable biocatalytic systems. This comprehensive guide aims to support researchers and industries in selecting and optimizing immobilization techniques for diverse applications in pharmaceuticals, food processing, and fine chemicals.

Microspheres with well-defined hollow structures have been attracting interest due to their unique morphology and fascinating properties. Herein, a strategy for morphology and size control of hollow polymer@silica microspheres is proposed. Multilayer core-shell polymer microspheres, containing substantial carboxyl groups inside, evolve into microspheres with a 304 nm hollow structure after alkali treatment, which are used to construct hollow polymer@silica microspheres by coating the inorganic layer using the layer-by-layer (LBL) and sol-gel methods, respectively. The inorganic shell thickness of hollow polymer@silica microspheres can be adjusted from 15 nm to 33 nm by the self-assembled layers in the LBL method and from 15 nm to 63 nm by the dosage of precursor in the sol-gel method. Compared to the LBL method, the hollow polymer@silica microspheres prepared via the sol-gel method have a uniform and dense inorganic shell, thus ensuring the complete spherical morphology of the microspheres after calcination, even if the inorganic shell thickness is only 15 nm. Moreover, the hollow polymer@silica microspheres prepared via the sol-gel method exhibit improved compression resistance and good opacity, remaining intact at 16,000 psi and providing the corresponding coating with transmittance lower than 35.1%. This work highlights the morphology regulation of microspheres prepared by different methods and provides useful insights for the design of composites microspheres with controllable structures.

Physalis alkekengi L. fruit polysaccharides can reduce blood sugar, regulate blood lipids, and improve intestinal flora structure. However, the specific polysaccharide components exerting these effects are unclear. In this study, we extracted, separated, purified, and characterized the P. alkekengi polysaccharides Phy-1a, Phy-1b, and Phy-1c. Ion chromatography showed that Phy-1b was mainly composed of rhamnose, arabinose, galactose, glucose, and xylose at a molar ratio of 3.0:19.8:47.5:20.9:8.8, and Phy-1c was composed of rhamnose, arabinose, galactose, glucose, xylose, mannose, ribose Galactosamine hydrochloride and Glucosamine hydrochloride at a molar ratio of 10.4:7.9:22.8:30.5:4.6:4.4:19.4:3.9:5.8. Neither of these polysaccharides contained uronic acid, indicating their neutral property. Methylation analysis and nuclear magnetic resonance spectroscopy showed that Phy-1b was mainly composed of terminal sugars (1-Araf); 1,5-Araf; 1,4-Xylp; 1-Glcp; 2,4-Rhap; 1,3-Glcp; 1,4-Galp; 1,4-Glcp; 1,3-Galp; 1,6-Glcp; 1,3,6-Glcp; and 1,4,6-Galp at a molar ratio of 5.2:7.1:7.8:13.7:6.3:11.2:7.0:16.3:7.4:6.0:6.8:5.3, with the main chain being →2)-α-L-Rhap-(1→4)-β-d-Galp-(1→4)-β-d-Galp-(1→[3)-β-d-Glcp-(1]2→3)-β-d-Glcp-(1→[4)-β-d-Glcp-(1]2→ and the branched chains being β-L-Araf-(1→5)-β-L-Araf-(1→, β-d-Glcp-(1→4)-β-d-Xylp-(1→ 3)-β-d-Galp-(1→, and β-d-Glcp-(1→6)-β-d-Glcp-(1→. The three fragments, respectively, pass through the O-4 key of →2,4)-α-l-Rhap-(1→, O-6 key of →4,6)-β-d-Galp-(1→, and O-6 of →3,6)-β-d-Glcp-(1→ connected to the main chain. These results provide a reference for enhancing the utilization value of P. alkekengi resources to promote its high-value and efficient processing.

Aquilaria spp. are a highly valuable plant species found in the Chinese herbal medicine and agarwood fragrance supplement industries for fumigation, combustion and perfume. The phytochemical composition of agarwood oils (extracts) was derived from Aquilaria sinensis and its subspecies 'Qi-Nan' using supercritical CO₂ extraction technology. Gas chromatography connected with a mass spectrometry apparatus was employed for qualitative and quantitative analyses. Comparing the agarwood oils from six planting areas, 12 common components were obtained, among which sesquiterpenes and chromones had the highest relative content. Genetic and environmental factors had the greatest impact on the three chromones, especially on 2-phenyl-4H-chromen-4-one. According to the PCA and PLS-DA models, the 'Qi-Nan' was derived from a variety selected from the native A. sinensis, and the difference in the volatile components was able to indirectly prove that it was genetically heterogeneous with the native A. sinensis. Using the 73 components obtained from GC-MS analysis, the VIP values and S-plots were generated using the OPLS-DA model. Seven components with VIP values > 1.0 were selected from two groups of agarwood oils of the native A. sinensis and 'Qi-Nan' subspecies. In addition, by analyzing 12 common components, the differential components with VIP values > 1 were 2-phenyl-4H-chromen-4-one and 2-(4-methoxyphenethyl)-4H-chromen-4-one. Chromones were the main component of agarwood oils extracted by supercritical CO₂, and 2-phenyl-4H-chromen-4-one could be used as a volatile marker, especially in the 'Qi-Nan' subspecies, where this marker exhibited more prominent characteristics.