Search Results (9,059)

Herein, we present the synthesis of N-(4-fluorobenzyl)-N’-(4-fluorobenzylidene)-4-methylbenzenesulfonohydrazide. The compound has been thoroughly characterized through melting-point determination, ¹H and ¹³C NMR spectroscopy and mass spectrometry. The structure was unequivocally determined by X-ray analysis. The comprehensive analytical data obtained from these techniques confirm the successful preparation and structural integrity of the newly synthesized molecule. Full article

Idelalisib (IDE) is a marketed chiral anticancer drug administered as the S-enantiomer, requiring sensitive monitoring of the R-enantiomer to ensure enantiomeric purity. However, no dedicated capillary electrophoresis (CE) method has been reported for trace-level quantification of R-IDE. In this study, a cyclodextrin-mediated CE method was developed for reliable detection of the R-enantiomer at the 0.1% level (LOD 2 µg/mL; LOQ 5 µg/mL). Systematic screening identified hydroxypropyl-β-cyclodextrin (HP-β-CD) with an intermediate degree of substitution (DS~6.8) as the optimal chiral selector, providing efficient enantioseparation (R_s up to 4.3). The method was validated according to ICH Q2(R2) guidelines, demonstrating suitable precision, accuracy, and robustness. Complementary NMR studies revealed hindered rotation of the 3-phenyl moiety and elucidated the molecular basis of enantioselectivity. Complexation with β-CD and HP-β-CD produced clear diastereomeric differentiation in both ¹H and ¹⁹F NMR spectra, while the simplified ¹⁹F NMR profiles enabled direct enantiomer discrimination. NOESY and ROESY experiments demonstrated distinct inclusion modes, with HP-β-CD accommodating both the fluorinated aromatic ring and the 3-phenyl moiety. These interactions may account for the superior enantioseparation observed with HP-β-CD of intermediate DS. Our validated CE method addresses the distomer determination while NMR insights provide mechanistic understanding of the chiral recognition. Full article

Background/Objectives: Parkinson’s disease (PD) exhibits marked sexual dimorphism, with a higher incidence and earlier onset in men than in women. However, the impact of biological sex on systemic molecular alterations in PD remains poorly understood. This pilot study aimed to identify sex-specific circulating signatures associated with PD. Methods: Serum samples from a selected cohort of PD patients and healthy controls (HC) of both sexes were analyzed using an integrated biochemical and ¹H NMR-based metabolomic approach. Oxidative stress markers, antioxidant proteins, inflammatory mediators, matrix metalloproteinases, α-synuclein species, and circulating antibodies were evaluated. Results: This analysis indicated that, while global oxidative stress markers were unchanged, sex-related differences in antioxidant pathways were observed as suggested by the reduced Nrf2 expression observed in PD females and increased IL-6 levels, above all in male PD patients. MMP3 levels were significantly higher in female PD patients compared with males. Male patients showed higher levels of 52 kDa protease-resistant α-synuclein species, while females exhibited increased antibody titers against both monomeric and aggregated forms. Metabolomic profiling suggested a disease-associated metabolic remodeling in PD, with distinct sex-related metabolic signatures and a more pronounced and widespread metabolic dysregulation in males. Conclusions: These findings suggest that biological sex may contribute to systemic molecular heterogeneity in PD, with trends indicating more pronounced inflammatory and metabolic alterations in males and distinct immune-related responses in females. Given the exploratory nature of the study and the limited sample size, these observations should be interpreted cautiously and require validation in larger, independent cohorts. Nevertheless, the results support the importance of considering sex-related molecular differences in future biomarker studies and precision medicine approaches for PD. Full article

Three new hybrid bis(salicylaldiminato)/calix[⁴]arene ligands H₄L1–H₄L3 have been synthesized and investigated with regard to their coordination behavior toward the UO₂²⁺ cation. The ligands H₄L1 and H₄L2, derived from bis-1,3-amino-ethoxy-functionalized calix[⁴]arenes and 3-methoxy-2-hydroxy-salicylaldehydes, react readily with uranyl nitrate in the presence of NEt₃ to support mononuclear neutral complexes with a 1:1 metal:ligand stoichiometry, namely [UO₂(H₂L1)] (6) and [UO₂(H₂L2)] (7). Ligand H₄L3, with an additional alanyl linker connecting the bis(2-amino-ethoxy)-calix[⁴]arene backbone and the 3-methoxy-2-hydroxy-salicylaldehyde arms, supports a neutral, mixed-ligand dinuclear uranyl complex [(UO₂)₂(MeO)₂(H₂L3)] (8). The ligands H₄L1 and H₄L2 act as pentadentate O₄N ligands for the UO₂²⁺ ion to produce a distorted pentagonal bipyramidal coordination environment (O₆N donor set). The ligand H₄L3 supports a binuclear [UO₂(μ-OMe)₂UO₂]²⁺ core unit, whose terminal coordination sites are occupied by the donors of the two pendant arms of H₄L3. The spectroscopic properties (NMR, IR, UV-Vis, ESI-MS) suggest that the complexes 6 and 7 retain their integrity in solution state. The structures are further stabilized by intramolecular hydrogen bonding interactions, as implied by computational analyses (NCI plots). These findings provide valuable insight into the influence of spatial flexibility and donor arrangement on the uranyl coordination chemistry of calix[⁴]arene-based ligand systems. Full article

Pixian Doubanjiang (PXDB) is a traditional Chinese fermented condiment whose characteristic aroma and taste are strongly influenced by fermentation conditions. This study aimed to systematically compare the flavor profiles of PXDB produced via traditional open fermentation (TOF) and industrial closed fermentation (ICF), aiming to elucidate the chemical basis of sensory divergence and provide scientific support for industrial process optimization. In this study, PXDB samples were evaluated using sensory evaluation, GC-IMS, ¹H-NMR metabolomics, and multivariate statistical analysis. Sensory evaluation revealed that ICF exhibited a stronger soy sauce-like aroma, alcohol note, and umami intensity, whereas TOF and ICF showed comparable sweetness, sourness, chili-like aroma, and roasted aroma. GC-IMS putatively identified 126 volatile compounds, and multivariate analyses demonstrated a clear separation between the two fermentation modes. Based on combined criteria of VIP > 1, FDR-adjusted p < 0.05, and |fold change| > 2, 35 differential volatile compounds were identified. ICF was characterized by higher levels of esters, particularly ethyl esters, and selected ketones, while TOF showed enrichment of higher alcohols, terpenes, and sulfur compounds. ¹H-NMR analysis identified 54 non-volatile metabolites, of which 16 differed significantly between TOF and ICF, mainly involving amino acids, organic acids, and carbohydrates. Pathway analysis highlighted branched-chain amino acid and glutamate-related metabolism as key contributors to flavor divergence. Correlation analysis further revealed that soy sauce-like aroma and umami perception were strongly associated with amino acid-derived metabolites, esters, sulfur-containing compounds, and branched-chain aldehydes, highlighting the coordinated contribution of volatile and non-volatile compounds to flavor differentiation. Overall, fermentation mode was found to reshape PXDB flavor through coordinated modulation of volatile and non-volatile metabolism, providing experimental insight for improving industrial fermentation quality. Full article

A novel synthetic approach was developed to synthesize 6-methoxy substituted imidazo[1,2-a]pyridine derivatives, with the objective of obtaining analogs of previously identified antileishmanial hit compounds. The nitration of 8-bromo-2-(chloromethyl)-6-methoxyimidazo[1,2-a]pyridine under classical nitric acid/sulfuric acid conditions resulted in selective nitration at position 5 and the corresponding 3,5-dinitrated derivative. The structures of these compounds were established through a combination of experimental methods, including ¹H and ¹³C NMR, HRMS, HSQC, and HMBC experiments. These structural determinations were subsequently confirmed through single-crystal X-ray diffraction. These compounds represent the first examples of 5-nitrated and 3,5-dinitrated 6-methoxyimidazo[1,2-a]pyridines. Full article

Radix Paeoniae Alba, the dried root of Paeonia lactiflora Pall., contains characteristic monoterpene glycosides, but efficient recovery of these polar constituents remains challenging. This study developed an ionic liquid-assisted sequential ultrasound–microwave extraction method and evaluated paeoniflorin, oxypaeoniflorin and albiflorin by HPLC as multi-marker responses. Among the ionic liquids tested, 1-propyl-3-methylimidazolium dihydrogen phosphate showed the best extraction response. Box–Behnken response surface optimization gave practical extraction conditions of a solid-to-liquid ratio of 1:26 g/mL, ionic liquid concentration of 0.12 mol/L and ultrasound time of 22 min. Under these conditions, paeoniflorin and total marker glycosides reached 29.12 and 34.98 mg/g dry material, respectively, representing increases of 32.4% and 34.5% compared with conventional reflux extraction. UPLC-QTOF-MS profiling provided complementary chemical profile information for the optimized extract and tentatively annotated Paeonia-related monoterpene glycoside derivatives, galloylated glucose derivatives and polyphenolic constituents. Electrostatic potential, SAPT and non-covalent interaction analyses, supported by ¹H NMR chemical shift perturbation, suggested possible hydrogen bonding, electrostatic and dispersion interactions between paeoniflorin and the selected ionic liquid. These results support the optimized process as an efficient extraction approach and provide molecular interaction insights into ionic liquid-assisted recovery of monoterpene glycosides. Full article

Aiming at severe soil secondary salinization, poor water retention and insufficient salt tolerance of conventional acrylic-based modifiers in arid and semi-arid regions of China, a poly(ethylene glycol) maleate citrate (PEGMC) crosslinking monomer was synthesized through esterification, and a dual covalent–hydrogen crosslinked P(PEGMC/AA) hydrogel was fabricated via free radical copolymerization with acrylic acid (AA). The hydrogel was characterized by NMR, FTIR, SEM, TGA and elemental mapping, while its binding mechanism with saline–alkali ions was elucidated through DFT calculations and molecular dynamics simulations. Its amelioration performance was evaluated through swelling, soil water retention, desalination and pot germination experiments. The hydrogel exhibited outstanding water absorbency, salt resistance and dry–wet cycling stability, with swelling ratios of 712 g/g in deionized water and 285 g/g in 0.9% NaCl solution, and remained 200 g/g after four dry–wet cycles. It enhanced soil water retention remarkably (over 93% after 72 h). At 0.30% dosage, soil salt content declined from 7.1 g/kg to 1.3 g/kg with desalination efficiency exceeding 80%, owing to porous physical adsorption and chemical chelation toward Na⁺, Ca²⁺ and Mg²⁺, with a binding energy of −136.936 kJ/mol. Pot tests revealed that crop germination rate rose from 19% (blank) to 75% under severe saline–alkali stress. Meanwhile, the hydrogel inhibited nutrient leaching and favored soil-water conservation. This work first incorporated PEGMC monomer into agricultural hydrogels to construct a stable dual crosslinked network, clarifying its synergistic mechanisms for salt fixation and water retention macroscopically and microscopically. It provides a promising functional material and theoretical basis for green, efficient in situ amelioration of dryland saline–alkali soil. Full article

Chronic inflammation and metabolic dysregulation of heart failure (HF) often result in sarcopenia. The combined effect of Mediterranean diet (MD) and omega-3 polyunsaturated fatty acids on the advanced lipidomic profile of HF patients remains poorly defined. Objective: Our objective was to analyze the specific effects of a MD plus omega-3-enriched oral nutritional supplements (MD+ONS) versus MD alone on the metabolic lipid profile of patients with HF, stratified by sarcopenia status. Methods: In this prospective, open-label, randomized controlled trial, 38 patients with HF were assigned to MD alone or MD+ONS (24 weeks). Advanced lipoprotein profiling (triglycerides, cholesterol, particle size, and concentration for VLDL, LDL, and HDL subclasses) was performed using 2D ¹H-NMR spectroscopy. Results: At baseline, NT-proBNP levels correlated positively with ω6/ω7ω9 fatty acids and IDL-TG (p < 0.05). Over 24 weeks, VLDL-C, VLDL-TG, and VLDL-P significantly decreased in the whole cohort (p < 0.001). However, stratified analysis revealed that in patients with sarcopenia, these reductions were primarily driven in the MD group (p < 0.01). Conversely, in patients without sarcopenia, the MD+ONS group showed significant reductions in VLDL-TG, VLDL-P, and VLDL-Z (p < 0.05). Regarding intermediate lipoproteins, IDL-C significantly increased in the MD group (p < 0.05) but not in the MD+ONS group. In the LDL fraction, total LDL-P and small LDL-P decreased in the MD group (p < 0.05), while medium LDL-P increased across both groups (p < 0.01). Total HDL-P decreased (p < 0.05), yet large HDL-P significantly increased in the whole cohort and the MD group (p < 0.05). No significant changes were observed in structural lipids or total fatty acid families. Conclusions: MD+ONS induces lipidomic shifts that are significantly modulated by baseline sarcopenia. The intervention appears to stabilize VLDL and IDL levels in patients with sarcopenia compared to diet alone, while promoting a more favorable VLDL reduction in individuals without sarcopenia, suggesting that early nutritional support for improving body composition is a critical determinant of the metabolic response to specific interventions in patients with HF. Full article

A biological/synthetic hybrid graft copolymer was obtained by grafting poly(acrylic acid) (PAA, synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization) to amylopectin (AMP). The novel graft copolymer presents amphiphilic properties due to the inherent insolubility of AMP in water and was further utilized as a mediator for the synthesis of gold nanoparticles (AuNPs) following an environmentally friendly in situ procedure. The AMP-g-PAA copolymer formation by the interaction of the PAA end groups with the C(6)-OH groups on an AMP backbone was confirmed by Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) and 1D (proton (¹H NMR) and carbon (¹³C NMR) nuclear magnetic resonance, and Distortionless Enhancement by Polarization Transfer (DEPT)) and 2D (correlation (COSY) and heteronuclear single quantum coherence (HSQC)) spectroscopies. The calculated degree of substitution of 1.17 suggests that the grafting was done at one OH from the three in an anhydroglycosidic unit (AGU) (preferably at that in C6 position), with a mean grafting efficiency of 76%. Additional information obtained using thermogravimetric analysis shows that the thermal decomposition of AMP-g-PAA occurs in two steps, with a residual mass of ~16 wt% at 700 °C, higher than AMP or PAA, indicating increased thermal stability of the copolymer. Dynamic and electrophoretic light scattering (DLS and ELS) measurements were used to determine the hydrodynamic size and ionic charge of the AMP-g-PAA self-assemblies in aqueous solution as well as their stability. The AMP-g-PAA was subsequently tested as a reducing agent in the environmentally friendly synthesis of AuNPs in aqueous solution, at different incubation temperatures, reaction duration, and inorganic/polymer weight ratios. The development of the surface plasmon resonance band of AuNPs, observed in UV–vis spectra, was consistently monitored over the reaction time. DLS analysis indicated time-dependent changes in the AuNPs’ particle size distributions, while scanning transmission electron microscopy confirmed that the AuNPs formed at the inorganic/polymer weight ratio of 0.36 and at 60 °C were predominantly well-dispersed, spherical-shaped nanoparticles. The AuNPs synthesized in situ within the copolymer matrix did not introduce additional cytotoxicity compared to the parent copolymer alone, with the composites representing a promising safety baseline for further investigation in biomedical applications. Full article

Novel steroidal heterocyclic derivatives were prepared from cholesterol, stigmasterol, and diosgenin scaffolds via concise, reagent-efficient synthetic routes. Two 1,3-oxathiolan-5-one derivatives bearing cholest-5-ene (7) and stigmasta-5,22-diene (8) cores were obtained from the corresponding steroidal ketones through hydrazone formation, phenyl isothiocyanate addition, and S-selective cyclization with chloroacetic acid in refluxing toluene. An aminothiazole–diosgenin hybrid (12) was independently prepared via regioselective α-bromination of an oxidized diosgenin intermediate followed by condensation with thiourea in ethanolic sodium ethoxide. The newly synthesized target compounds were characterized by FT-IR, ¹H- and ¹³C-NMR spectroscopy, ESI mass spectrometry, and elemental (CHNS) analysis. The disc-diffusion assay against S. aureus and E. coli was retained only as a preliminary qualitative screen because no positive antibiotic control or MIC determination was included. Within this limited screen, compound 12 produced measurable 8.5–9.0 mm inhibition zones against both strains, supporting their prioritization for future standardized antimicrobial testing rather than establishing comparative potency. Full article

3-(4-hydroxynaphthalen-1-yl)-3-(1-hydroxynaphthalen-2-yl)isobenzofuran-1(3H)-one is a previously unknown derivative of the well-known acid/base indicator naphtholphthalein. We report the synthesis and the molecular structure of the title compound, as determined by single-crystal X-ray diffraction. ¹H and ¹³C NMR spectroscopy data, IR spectroscopy data, and mass spectrometry data are provided. Full article

Marine medicinal algae represent a valuable reservoir of bioactive metabolites for anticancer drug discovery, yet the efficient identification of target-relevant compounds from chemically complex marine matrices remains challenging. In this study, an integrated cathepsin B-oriented strategy was developed to discover, prioritize, isolate, and validate antitumor metabolites from the brown alga Sargassum polycystum. Affinity ultrafiltration LC-MS was first applied to screen CTSB-binding constituents from the crude extract, followed by molecular docking, molecular dynamics simulation, and gray relational analysis for multidimensional candidate prioritization. Seven CTSB-binding metabolites were characterized, including chlorogenic acid, caffeic acid, cynarin, loliolide, taxifolin, senkyunolide H, and dihydroactinidiolide, with binding degrees of 73.99–85.61% at 2.5 U/mL CTSB. Molecular docking showed predicted binding affinities ranging from −6.3 to −9.4 kcal/mol, compared with −10.2 kcal/mol for the positive control CA-074Me. Integrated computational and biological evaluation identified caffeic acid, cynarin, and taxifolin as the top-ranked candidates. Preparative recovery was then achieved using counter-current chromatography combined with semi-preparative HPLC, and the isolated compounds were structurally identified by LC-MS/MS and NMR. Cellular assays in NCI-H1975 cells suggested that these metabolites reduced CTSB-associated enzymatic activity and intracellular CTSB-related fluorescence signals to different extents, with phenolic acid-type compounds exhibiting comparatively stronger effects. At the extract level, S. polycystum dose-dependently suppressed NCI-H1975 xenograft tumor growth, with inhibition rates of 48.78%, 36.58%, and 22.86% in the high-, middle-, and low-dose groups, respectively, without evident hepatorenal histopathological toxicity. This effect was associated with reduced CTSB, Ki-67, and Bcl-2 staining, increased Bax staining, enhanced apoptosis, and ultrastructural alterations in tumor tissues. Overall, this study provides a practical CTSB-oriented workflow for discovering antitumor metabolites from marine medicinal algae and supports further investigation of S. polycystum as a potential source of anti-NSCLC candidates. Full article

The cyclobutane ring has attractive properties as a scaffold in medicinal chemistry but is underused, potentially due to the limited methods available for synthesising highly functionalised cyclobutanes. This short note describes the synthesis of the 1,3-cis disubstituted cyclobutane, methyl (S)-3-((1r*,3R*)-3-((1H-indol-3-yl)methyl)cyclobutane-1-carboxamido)-2-(phenylsulfonamido)propanoate using a one-pot thermal stepwise cycloaddition reaction and its characterisation by NMR spectroscopy and HRMS. Full article