Molecules最新文献

Derivatives of 4,7-diphenyl-2,1,3-benzothiadiazole are highly stable compounds that fluoresce efficiently both in solutions and in the crystalline state. Thanks to their wide range of remarkable optoelectronic characteristics, they can rightly be called smart materials. This paper presents the results of an investigation into the polymorphism of 4,7-bis(4-(trimethylsilyl)phenyl)-2,1,3-benzothiadiazole (TMS-P-BTD) crystals under weakly and strongly non-equilibrium crystallization conditions from the vapor phase (PVD), solutions, and melt. Using single-crystal X-ray diffraction analysis at room temperature, two new polymorphic crystal modifications have been identified: orthorhombic II (sp. gr. Pnaa, Z/Z' = 12/1.5) and triclinic III (sp. gr. P-1, Z/Z' = 8/4). It was determined that the densest polymorph III melts at 154 °C. The least dense orthorhombic polymorph II dominates under kinetic growth conditions, melts independently at 151 °C, but transforms into polymorph III upon prolonged annealing. It has been established that the previously identified monoclinic polymorph I (P2₁/c, Z/Z' = 32/8) transforms into polymorph III upon heating in the range of 75-110 °C. In the series of polymorphs I→II→III, a blue shift in the fluorescence spectrum maximum is observed: approximately 375 cm^-1 for polymorph II and ~635 cm^-1 for polymorph III relative to the position of the maximum λ_max,I = 497 nm for polymorph I. The observed spectral-fluorescence features of the TMS-P-BTD crystal polymorphic phases are consistent with the structure of the flattest molecular conformers within the crystal unit cells.

An anthraquinone chromophore displaying a vivid violet color in solution was synthesized and it was thoroughly characterized both spectroscopically and electrochemically, along with its X-ray crystallography. Single crystal X-ray analysis of the chromophore revealed a nearly planar π-conjugated framework with short intermolecular contacts. Cyclic voltammetry revealed two consecutive one-electron reductions, corresponding to the formation of its radical anion and dianion. The spectroelectrochemistry of the chromophore confirmed two distinct and reversible color changes with the stepwise electrochemical reduction. These were quantified via the CIE L a* b* color space. Large optical differences (98%) between the bleached and colored states were observed along with a coloration efficiency of 698 cm²/C. These parameters confirm the anthraquinone is an ideal electrochrome: capable of reversibly switching its colors with applied potential. The three color changes and color bleaching associated with the neutral, radical anion, dianion, and cation, respectively, are also of interest for extending the palette of colors of molecular electrochromes toward panchromatic color tuning with molecular structure for use in smart windows and displays.

The development of microcapsules for the controlled release of active substances offers an innovative strategy in restorative dentistry, expanding the possibilities beyond traditional methods. In this study, microcapsules loaded with triethylene glycol dimethacrylate (TEGDMA) and different concentrations of hydroxyapatite (HAP)-0%, 5%, 10%, 15%, and 20%, referred to as M0, M5, M10, M15, and M20-were synthesized through in situ polymerization within an oil-in-water emulsion. Their morphology, size, and nanostructure were examined using scanning electron microscopy (SEM) and atomic force microscopy (AFM). Fourier-transform infrared spectroscopy (FTIR) confirmed the presence of characteristic chemical bonds, whereas high-performance liquid chromatography (HPLC) quantified residual TEGDMA monomer. Low-field nuclear magnetic resonance (NMR) further confirmed the presence and the distribution of the liquid healing agent inside the microcapsules. The analyses indicated that microcapsules incorporating 20% hydroxyapatite exhibited superior structural organization and improved shell integrity, highlighting their potential in the remineralization processes. Overall, these results support the potential of HAP-TEGDMA microcapsules for incorporation into dental composites to facilitate microcrack repair and promote dental tissue regeneration.

CD38 is a multifunctional enzyme that plays a pivotal role in NAD⁺ metabolism and calcium signaling, and its abnormal activity is closely associated with multiple myeloma, age-related metabolic decline, neurodegenerative diseases, and other disorders. Although monoclonal antibodies such as daratumumab have been approved for clinical application, their inherent limitations necessitate the development of novel small-molecule CD38 inhibitors. In this study, we employed DNA-encoded library (DEL) technology for the high-throughput screening of CD38 inhibitors, using a DEL library containing more than 100,000 unique compounds to screen against recombinant human CD38. A total of 1043 enriched compounds were initially identified, and after rigorous validation and screening to exclude non-specific binding and previously reported active compounds, eight hit compounds with diverse chemical scaffolds were obtained, among which Fenbendazole-a clinically approved antiparasitic drug-was included. Surface plasmon resonance (SPR) assays confirmed the direct binding of these hit compounds to CD38, with dissociation constants (KD) ranging from 7.74 × 10^-5 M to 2.15 × 10^-4 M. Fluorescence-based enzymatic activity assays demonstrated that these compounds exert dose-dependent inhibitory effects on both the hydrolase (with ε-NAD as substrate) and cyclase (with NGD as substrate) activities of CD38. Further structure-activity relationship (SAR) analysis of Fenbendazole analogues revealed the critical structural features that regulate CD38 inhibitory potency, and Flubendazole was found to exhibit excellent inhibitory activity, with an IC₅₀ of 14.78 ± 4.21 μM against CD38 hydrolase and 26.31 ± 3.40 μM against cyclase. Molecular docking and 100 ns molecular dynamics (MD) simulations further elucidated the molecular mechanism of CD38 inhibition by lead compounds, confirming that van der Waals interactions are the main driving force for the binding of small-molecule ligands to CD38, with conserved aromatic residues in the active site mediating ligand recognition. This study validates DEL technology as an efficient and reliable platform for the discovery of CD38 inhibitors, and the identified lead compounds-especially Fenbendazole and its analog Flubendazole-provide valuable molecular scaffolds for the further structural optimization of CD38 inhibitors. These findings lay a solid foundation for the development of novel therapeutic agents for the treatment of CD38-associated diseases.

In this study, the biological activities of extracts obtained from Ramaria obtusissima were optimized using response surface methodology (RSM) and artificial neural networks-genetic algorithm (ANN-GA) approaches, and the chemical and biological profiles of the obtained extracts were evaluated with a holistic approach. Antioxidant potential was determined using FRAP, DPPH, TAS, TOS, and OSI parameters. It was found that the extract optimized with ANN-GA had significantly higher FRAP (242 ± 3 mg Trolox equivalent/g), TAS (6.64 ± 0.04 mmol/L), and DPPH (154 ± 3 mg Trolox equivalent/g) values compared to the RSM extract, while its OSI value was lower. Anticholinesterase activities were evaluated using IC₅₀ values, and it was determined that the ANN-GA extract exhibited a stronger inhibitory effect on acetylcholinesterase (95 ± 2 µg/mL) and butyrylcholinesterase (125 ± 3 µg/mL) compared to the RSM extract. Antiproliferative effects were investigated in A549, MCF-7, and DU-145 cell lines, and a significant and dose-dependent suppression of cell proliferation was observed in all three cell lines, particularly at concentrations of 100 and 200 µg/mL. The chemical profile was determined using LC-MS/MS and GC-MS techniques. Higher levels of phenolic compounds such as gallic acid (6694.5 ± 4.9 mg/kg), caffeic acid (3374.8 ± 4.9 mg/kg), and quercetin (1563.1 ± 2.3 mg/kg) were found in the ANN-GA extract. GC-MS analyses showed that the ANN-GA extract has a richer lipophilic component profile in terms of biologically active fatty acids and ester derivatives. The findings reveal that AI-assisted optimization offers a powerful and effective approach to enhancing the biological efficacy of mushroom-derived natural products.

This study investigated the effect of solvent polarity on extraction yield, phytochemical composition, antioxidant activity, and α-amylase inhibition of Elaeagnus angustifolia L. leaf extracts to evaluate their antidiabetic potential. Extraction yields varied with solvent polarity, with the hydroethanolic extract showing the highest (18.00%) and n-hexane the lowest (0.05%) yield. The n-butanol and ethyl acetate fractions contained the most phenolics (309.05 and 290.97 mg GAE/g), ethyl acetate was the richest in flavonoids (102.11 mg QE/g), and tannins were concentrated in dichloromethane (66.24 mg CE/g). HPLC revealed solvent-specific profiles: rutin and gallic acid dominated in n-butanol, quercetin in ethyl acetate, and 4-hydroxybenzoic and ferulic acids in dichloromethane, while chicoric acid appeared in hydroethanolic and n-hexane extracts. Antioxidant assays (DPPH, ABTS, and FRAP) showed strong activity in polar extracts, particularly hydroethanolic and ethyl acetate fractions. The n-hexane extract exhibited the highest α-amylase inhibition (IC₅₀ = 36.70 µg/mL), surpassing acarbose (IC₅₀ = 126.14 µg/mL), while other fractions were inactive (IC₅₀ > 400 µg/mL). Molecular docking highlighted rutin, chlorogenic acid, and chicoric acid as potential enzyme binders. These findings demonstrate the chemical diversity and significant bioactivities of E. angustifolia leaves, supporting their potential as natural antidiabetic agents.

Mucuna pruriens (L.) DC. (Fabaceae), commonly known as velvet bean, is an annual tropical legume widely distributed in India, Africa, and the Americas. It has a long history of use in traditional medicine for managing various health conditions. It is renowned for its anti-inflammatory, antimicrobial, aphrodisiac, and anti-Parkinson effects. The entire plant is considered health-promoting, particularly the seeds. They have been used for their neuroprotective, fertility-enhancing, and antioxidant effects. This review aims to compile all available information regarding the chemical composition of all parts of this medicinal plant. For this purpose, the complete databases of Google Scholar, Scopus, PubMed, and Web of Science available to date were utilized. All studies reported the presence of a diverse range of secondary metabolites, including phenolic compounds, such as phenolic acids, flavonoids, and tannins, as well as saponins and alkaloids. Most studies concentrated on the chemical characterization of the seeds, whereas the leaves, roots, and pods have received comparatively limited scientific attention. The seeds of M. pruriens are renowned for their high concentration of L-3,4-dihydroxyphenylalanine (L-DOPA), a metabolic precursor of dopamine. A large proportion of these studies originated from countries where M. pruriens naturally occurs. Few studies have been conducted on the chemical composition of velvet bean outside these regions. Despite the existing information on the chemical composition of M. pruriens. (seeds, leaves, and roots), further research beyond its natural habitat is required to gain a broader understanding of its chemical profile and pharmacological effects.

Current cancer treatments have significant limitations. Designing TPP⁺-modified, mitochondrial-targeted drugs can improve anticancer efficacy. Although wogonin exhibits antitumor activity, it has drawbacks, including poor solubility and limited distribution. This study designed and synthesized 27 derivatives, including nine novel wogonin triphenylphosphine derivatives that demonstrated in vitro antitumor activity. Mito-WO-8, one of these derivatives, exhibited potent activity against PC-3M cells (IC₅₀ = 3.19 μmol/L), demonstrating 15-fold higher potency than wogonin. Further analysis revealed that Mito-WO-8 accumulates more in mitochondria than wogonin and induces mitochondrial dysfunction, including increased reactive oxygen species, reduced membrane potential, and activation of the MPTP channel. Transcriptome and network analyses revealed that Mito-WO-8 activates the p38/MAPK pathway. Downregulation of p-MKK6 and p-p38, as well as upregulation of DDIT3 and cleaved caspase-3, were validated by Western blot (WB) and quantitative polymerase chain reaction (qPCR). Therefore, Mito-WO-8 enhances mitochondrial enrichment and induces mitochondrial damage. This process is associated with apoptosis and the activation of the ROS-p38/MAPK pathway. Additionally, the study found that Mito-WO-8 exhibits a stronger binding affinity for mitochondrial glycerol-3-phosphate dehydrogenase 2 (GPD2) than the parent compound (-9.6 kJ/mol vs. -6.6 kJ/mol), suggesting a potential interaction with GPD2. This finding establishes a foundation for further investigation into its targeted antitumor mechanism.

Royal jelly, a nutrient-rich bee product characterized by high water content and active components, is particularly susceptible to quality deterioration during storage. While temperature effects have been extensively documented, the specific role of light exposure in quality degradation remains largely unexplored. despite its relevance during production, handling, transportation, and display. This study systematically investigated the volatile organic compounds (VOCs) of royal jelly under different storage conditions using gas chromatography-ion mobility spectrometry (GC-IMS) combined with fingerprint analysis. Results from dual-column validation demonstrated that even short-term light exposure at 25 °C induced pronounced alterations in VOC profiles, triggering the accumulation of off-flavor aldehydes (e.g., hexanal, nonanal) and ketones, along with 2-furfural generated via Maillard reaction. Concurrently, characteristic fresh-aroma esters and alcohols were significantly depleted. Multivariate statistical analysis confirmed light exposure as the predominant factor driving quality deterioration, with temperature variation under dark conditions producing comparatively minor effects within the same short timeframe. This work provides the first systematic evidence establishing insights into early volatile changes in royal jelly and identifies key VOC markers that offer valuable insights for optimizing storage strategies and developing rapid quality monitoring protocols.

A simple, rapid, and cost-effective UV-Vis spectrophotometric method was developed and validated for the determination of levofloxacin in rat plasma to support the evaluation of a novel antimicrobial mesh implant containing levofloxacin, chitosan, gelatin, tinctura propolis, citric, acid and glycerin. Plasma samples were treated with 0.1 M HCl, and absorbance was measured at 290 nm. The method was validated according to FDA and ICH guidelines, including assessments of linearity, sensitivity, accuracy, precision, and specificity. The calibration curve was linear over the concentration range of 2.5-12.5 μg/mL (R² = 0.999, p < 0.001). The limit of detection and limit of quantification were 0.21 μg/mL and 0.62 μg/mL, respectively. Intra- and inter-day precision showed low relative standard deviation values (0.2% and 0.25%), while recovery ranged from 94.8% to 96.4%, confirming acceptable accuracy. No significant interference from plasma matrix components was observed. Compared with chromatographic techniques, the proposed method provides an accessible alternative for routine bioanalysis and therapeutic monitoring. The validated assay is suitable for assessing prolonged levofloxacin release from implantable drug delivery systems in preclinical studies.