Search Results (850)

Lung cancer (LC) remains the leading cause of cancer-related death worldwide, largely due to late-stage diagnosis and the limited performance of current screening strategies. In this preliminary study, headspace solid-phase microextraction coupled with gas chromatography–mass spectrometry (HS-SPME/GC-MS) was used to comprehensively characterize the urinary volatilome of LC patients and healthy controls (HCs), with the dual aim of defining an LC-associated volatilomic signature and identifying volatile organic metabolites (VOMs) with discriminatory potential. A total of 56 VOMs spanning multiple chemical classes were identified, revealing a distinct metabolic footprint between groups. LC patients exhibited markedly increased levels of terpenoids and aldehydes, consistent with heightened oxidative stress, including lipid peroxidation, and perturbed metabolic pathways, whereas HCs showed a predominance of sulphur-containing compounds and volatile phenols, likely reflecting active sulphur amino acid metabolism and/or microbial-derived processes. Multivariate modelling using partial least squares-discriminant analysis (PLS-DA, R² = 0.961; Q² = 0.941; p < 0.001), supported by hierarchical clustering, demonstrated robust and clearly separated group stratification. Among the detected VOMs, octanal, dehydro-p-cymene, 2,6-dimethyl-7-octen-2-ol and 3,7-dimethyl-3-octanol displayed the highest discriminative power, emerging as promising candidate urinary biomarkers of LC. These findings provide proof-of-concept that HS-SPME/GC-MS-based urinary volatilomic profiling can capture disease-specific molecular signatures and may serve as a non-invasive approach to support the early detection of LC, warranting validation in independent cohorts and integration within future multi-omics diagnostic frameworks. Full article

Membrane rupture, induced by lipid peroxidation, is a severe threat to osmotic balance, as membrane pores contribute to ferroptosis, an iron-dependent cell death. To alleviate osmotic stress, membrane constituents dynamically reconstruct the membrane and interact with intracellular molecules. Tumor-derived acidosis shift glycolysis-dependent metabolism toward lipid metabolism, increasing polyunsaturated fatty acids (PUFAs). PUFAs enhance membrane fluidity but make cancer susceptible to lipid peroxidation. Also, the ionization of phospholipids under low pH can accelerate membrane rupture. This stress can be mitigated by the redistribution of cholesterol, which maintains tension–compression balance and acts as antioxidants. When excessive reactive aldehydes—byproducts of lipid peroxidation—overwhelm cholesterol’s protective role, lipid peroxides promote membrane cracks. Moreover, a deficiency in glutathione can alter cholesterol’s function, turning it into a pro-oxidant. In contrast, ceramide, derived from membrane lipids, indirectly prevents ferroptosis by facilitating cytochrome c release. This review integrates recent findings on how membrane components and environmental stressors influence ferroptosis. It also suggests potential therapeutic strategies. This could advance our understanding of ferroptosis in cancer. Full article

The anti-inflammatory scaffold 5-aminosalicylic acid, which is widely used in therapeutic applications, was chosen for the synthesis of N-[3-(hydrazinecarbonyl)-4-hydroxyphenyl]acetamide (1) to enhance its antibacterial properties. The condensation of hydrazide 1 with aromatic aldehydes provided hydrazone derivatives 2a–f, whereas cyclocondensation reactions and other related transformations afforded five-membered heterocycles, including pyrrole 3, pyrazole 4, pyrrolidinone 7, oxadiazoles 9, 10, thiadiazole 14, and triazole 15. Additional modifications yielded acetylhydrazine derivative 11, which was O-alkylated to analogue 12. Antibacterial evaluation showed stronger activity against Gram-positive bacteria such as S. aureus and MRSA than against Gram-negative strains of E. coli and S. Enteritidis, consistent with differences in cell membrane permeability. Notably, derivatives containing pyrrolidinone 7, thiosemicarbazide 13, and 1,3,4-thiadiazole 14 exhibited potent bactericidal activity against S. aureus and MRSA, while hydrazones 2b, 2c, 2f, pyrrole 3, and pyrrolidinone 7 exhibited activity against E. coli. These results provide a practical strategy for the discovery of heterocyclic compounds and emphasise the potential of functionalised 5-aminosalicylic acid derivatives as prime candidates for the development of broad-spectrum antibacterial agents. Full article

A transition-metal-free strategy for the synthesis of 2,3-dihydrobenzothiazin-4-one derivatives has been established. Using HI as the catalyst, various 2-substituted, N-substituted compounds and variations on the benzamide ring were synthesized in excellent yields via the reaction between 2-mercaptobenzamides and aldehydes. In addition, an easy experimental procedure, broad substrate scope, and excellent functional group tolerance demonstrate that this catalytic protocol provides a valuable complementary approach for accessing 2,3-dihydrobenzothiazin-4-one derivatives. Full article

The development of sustainable catalysts is the main objective in green chemistry approaches. In this study, a catalytically active polymer based on a tertiary amine was synthesized, functionalized with a photo-crosslinker, and structured into nanofibers via electrospinning technique with polycaprolactone (PCL) as a stabilizing additive. Subsequent photo-crosslinking yielded hierarchically porous polymers with high swelling properties and increased surface areas, thereby improving the accessibility of the immobilized catalytically active sites. The nanofiber mats were incorporated into a microfluidic reactor (MFR) setup and utilized as heterogeneous catalysts for the Knoevenagel reaction of malononitrile with different aldehydes. It was observed that the system demonstrated a substantial improvement in NMR yields (40–60%) and turnover frequencies (50–80 h⁻¹) in comparison to catalytical systems that had been previously published. Reusability studies showed reproducibility of NMR yields over up to three cycles. The obtained results demonstrate the potential of electrospun, photo-crosslinked nanofibers as efficient heterogeneous catalysts in microfluidic synthesis, thus contributing to more sustainable production of valuable malononitrile derivatives. Full article

High-risk neuroblastoma (NB) is an aggressive pediatric tumor characterized by pronounced biological heterogeneity and frequent development of chemoresistance, which critically limits therapeutic efficacy. Identifying novel anti-NB agents remains an urgent unmet need. To address this, we designed and synthesized 17 hybrid molecules by combining natural antioxidant scaffolds (coumarin, vanillin, and isovanillin) through an acyl-hydrazone linker. Several derivatives significantly reduced the viability of MYCN-amplified NB cells (HTLA-230) and their multi-drug resistant counterpart (ER) while not affecting human keratinocytes (HaCat). Among them, compounds 5, 9 and 12 selectively inhibited HTLA and ER growth (10–25%) without affecting HaCat, accompanied by robust ROS overproduction, particularly by 9 and 12 (up to 40%). None of these compounds induced apoptosis or ferroptosis. Instead, their antiproliferative effects were associated with senescence induction and, only for compound 5, with a decrease in clonogenic potential. Moreover, to further characterize compounds 5, 9, and 12, the analysis was extended across other human neuroblastoma cell lines. In parallel, the effects of the compounds on non-malignant cell lines were assessed to obtain an indication of their selectivity toward tumor cells. Compound 17, a structural analog lacking the second aromatic ring in the ex-aldehyde portion, displayed a distinct profile with a limited anticancer activity, underscoring the importance of this structural fragment for antiproliferative efficacy. Full article

Gastrodin is a bioactive component of traditional Chinese medicine, exhibiting anti-cancer, anti-inflammatory, antioxidant and neuroprotective properties. It has broad application prospects in health foods, pharmaceuticals and cosmetics. In recent years, the conversion of biomass-derived aldehydes into high-value-added chemicals has garnered widespread attention. In this study, gastrodin was biosynthesized via a dual-enzyme coupling system consisting of UGT_BL1-Δ60 and KpADH. Specifically, lignin-derived p-hydroxybenzaldehyde was used as the substrate. First, the glycosylation of p-hydroxybenzaldehyde by UGT_BL1-Δ60 yielded p-hydroxybenzaldehyde β-glucoside, generating the glycosylation reaction solution. Subsequently, bioreduction of the glycosylation product by KpADH produced gastrodin. Under the optimal reaction conditions (0.05 g/mL KpADH whole cells, 50 mM glucose, pH 7.5 and 30 °C) a gastrodin yield of 82.8% was achieved within 12 h. Moreover, both UGT_BL1-Δ60 and KpADH retained high catalytic activity after multiple reaction cycles. This study establishes a green and efficient biocatalytic approach for gastrodin synthesis, and also provides new insights into the high-value utilization of lignin. Full article

A novel series of Schiff bases (3a–3k), incorporating tranexamic acid (TXA) and phenol-derived aldehydes via imine linkers, was synthesized and structurally characterized. The antimicrobial activity of the compounds was evaluated against a range of clinically and environmentally relevant bacterial and fungal strains. Among them, derivatives 3i and 3k, bearing bromine and chlorine substituents on the phenol ring, exhibited the most potent antimicrobial effects, particularly against Penicillium italicum and Proteus mirabilis (MIC as low as 0.014 mg/mL). To elucidate the underlying mechanism of action, in silico molecular docking studies were conducted, revealing strong binding affinities of 3i and 3k toward fungal sterol 14α-demethylase (CYP51B), with predicted binding energies surpassing those of the reference antifungal ketoconazole. Additionally, UV-Vis and fluorescence spectroscopy assays demonstrated good stability of compound 3k in PBS and its effective binding to human serum albumin (HSA), respectively. ADMET and ProTox-II predictions further supported the drug-likeness, low toxicity (Class 4), and favorable pharmacokinetic profile of compound 3k. Collectively, these findings highlight TXA–phenol imine derivatives as promising scaffolds for the development of next-generation antimicrobial agents, particularly targeting resistant fungal pathogens. Full article

This work aimed to synthesize new derivatives of 2-hydrazinylpyridine-3-carbonitrile and to investigate their biological activity as safeners for the 2,4-D herbicide. The new 2-hydrazinylnicotinonitriles were obtained in high yields (up to quantitative) under mild conditions (25 °C, dioxane) by treating 4,6-diaryl-2-bromo-3-cyanopyridines with hydrazine hydrate. The latter were synthesized by brominating 2-(3-oxo-1,3-diarylpropyl)malononitriles, the Michael adducts, which are readily available from 1,3-diarylpropenones (chalcones) and malononitrile. An unusual side product of the bromination/carbocyclization was isolated and characterized; it consisted of co-crystals of 3-benzoyl-4-hydroxy-4-phenyl-2,6-di-(p-tolyl)cyclohexane-1,1-dicarbonitrile and 3-benzoyl-5-bromo-4-hydroxy-4-phenyl-2,6-di-(p-tolyl)cyclohexane-1,1-dicarbonitrile at a ~4:6 ratio. The new 2-hydrazinylnicotinonitriles react with halogen-containing aromatic aldehydes to form the corresponding hydrazones. The biological activity of the new nicotinonitriles was examined for their function as 2,4-D antidotes. It was found that, under laboratory conditions, eight of the synthesized compounds exhibited a notable antidote effect against 2,4-D on sunflower seedlings. Full article

This study aimed to investigate the influence of lipid oxidation intensity on histamine accumulation in fermented sausages and to identify specific lipid oxidation products potentially responsible for promoting histamine formation. Pork backfat was subjected to controlled oxidation at different temperatures to obtain varying degrees of oxidation and subsequently used in fermented sausage production. Histamine content was determined, and treatment groups exhibiting significant differences (50 °C, 60 °C, and 70 °C) were selected for further non-targeted metabolomic analysis. Multivariate statistical approaches, including PCA and OPLS-DA, were employed to screen and identify differential lipid oxidation products. The results revealed a significant positive correlation between the extent of lipid oxidation and histamine content (p < 0.05). Within the selected temperature range, the mean histamine contents were 22.97, 19.05, and 17.45 mg/kg for the 70 °C, 60 °C, and 50 °C treatments, respectively. A total of 33 lipid oxidation products were identified during ripening, predominantly aldehydes, ketones, alcohols, esters, acids, and alkanes. Pearson correlation analysis showed that four compounds—decanal, nonanal, hexanal, and 1-octen-3-ol—were strongly and positively correlated with histamine content (p < 0.01). These compounds were highlighted as key lipid-derived contributors potentially associated with elevated histamine levels. This study provides initial evidence that specific lipid oxidation products are closely linked to histamine accumulation in a real fermented sausage matrix. The findings offer a theoretical basis for reducing biogenic amine formation by controlling lipid oxidation during processing, which could have important practical implications for improving the safety of fermented meat products. Full article

Background: Rapidly growing mycobacteria (RGM) are microorganisms with variable pathogenicity, which can cause different clinical forms of mycobacterioses. They can form structured communities at the liquid-air interface and adhere to animate and inanimate solid surfaces, characterizing one of their most powerful mechanisms of resistance and survival, named biofilms. Objectives: Here, a novel series of sulfamethoxazole (SMTZ) Schiff bases were obtained by the condensation of the primary amine from SMTZ core with six different aldehydes to evaluate their antimicrobial and antibiofilm activities, as well as physicochemical and in silico characteristics. Methods: The compounds L1–L6 included: pyridoxal hydrochloride (L1), salicylaldehyde (L2), 3-methoxysalicylaldehyde (L3), 2-hydroxy-1-naphthaldehyde (L4), 3-allylsalicylaldehyde (L5), and 4-(diethylamino)salicylaldehyde (L6). MIC determination was performed against standard strains and seven clinical isolates. Time-kill assays, biofilm inhibition assays, atomic force microscopy, and peripheral blood mononuclear cell cytotoxicity assays were carried out. Density functional theory (DFT) calculations using quantum descriptors, Mulliken charges, Fukui functions, non-covalent interactions (NCI), and reduced density gradient (RDG), along with molecular docking calculations to DHS, LasR, and PqsR, supported the experimental trend. Results: The compounds L1–L6 showed a significant capacity to inhibit the growth of RGM, with MIC values in the range of 0.61 to 1.22 μg mL⁻¹, which are significantly lower than those observed for the parent compound SMTZ, demonstrating superior antimicrobial potency. To deepen antimicrobial activity assays, L1 was chosen for further evaluations and showed a significant ability to inhibit the growth of RGM in both planktonic and biofilm forms. In addition, atomic force microscopy views great changes in topography, electrical force, and nanomechanical properties of microorganisms. The cytotoxic assays with the peripheral blood mononuclear cell model suggest that the new compound may be considered as an antimicrobial alternative, as well as a safe substance showing selectivity indexes in the range of efficacy. Conclusions: Density functional theory (DFT) calculations were performed to obtain quantum descriptors, Mulliken charges, Fukui functions, non-covalent interactions (NCI), and reduced density gradient (RDG), which, with molecular docking calculations to DHS, LasR, and PqsR, supported the experimental trend. Full article

Ziziphi Spinosae semen (ZSS) is renowned for its rich nutritional composition and is traditionally consumed in China, Japan, and Korea, where it is widely incorporated into both medicinal diets and daily cuisine. To address the lack of systematic research comparing raw and fried ZSS, this study aimed to elucidate the compositional and functional changes induced by the frying process. This study systematically compared the chemical profiles and antioxidant activities of ZSS and fried ZSS using ultra-performance liquid chromatography–quadrupole–time-of-flight mass spectrometry (UPLC–Q–TOF–MS) and gas chromatography–ion mobility spectrometry (GC–IMS). A total of 92 non-volatile compounds and 43 volatile organic compounds (VOCs) were identified. Frying significantly promoted the formation of polar compounds such as flavonoids and saponins and increased the content of aldehydes and alcohols, thereby generating aromas characteristic of Maillard reactions and lipid oxidation. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) clearly distinguished the two groups in terms of their chemical composition and flavor characteristics. In addition, 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays demonstrated that the antioxidant capacity of fried ZSS was significantly higher than that of the raw sample (p < 0.05). These results indicate that the frying process reshapes the chemical properties and bioactivity of ZSS via multiple pathways, including glycoside hydrolysis, lipid oxidation, and Maillard reactions. Overall, this study establishes a scientific foundation for the development of functional foods derived from ZSS. Full article

This article is devoted to the synthesis and investigation of a family of new benzimidazole compounds with a propylsulfonate moiety, synthesized by condensation of salicylic aldehyde or its 5-substituted derivatives with 3-(2,3-dimethylbenzimidazol-1-ium-1-yl)propane-1-sulfonate. The structure of the obtained dyes was confirmed using NMR, FT-IR, and HRMS. Absorption and photoluminescence properties were studied in phosphate buffers over a wide pH range, and changes in the absorption and fluorescence spectra of DMSO solutions upon titration with DIPEA and HCl were also studied. It was found that all the target compounds possess pH-sensitive optical properties and can be used as fluorescent probes, while methoxycarbonyl-substituted derivative 3c demonstrated the most prominent optical and fluorescent response starting from pH ~ 4.5. The toxicity of the compounds was studied using whole-cell bioluminescent bacterial sensors. The effect on the biomass and metabolic activity of strains Staphylococcus aureus ATCC 6538-P FDA 209-P and Escherichia CDC F-50 bacterial biofilms was also investigated. In the final stage of the study, bioimaging experiments were carried out using the selected most promising dye 3c and biofilms. It was demonstrated that the dye can be excited by light with wavelengths of 458 nm or 750 nm in multiphoton mode. Importantly, when biofilms are incubated in the dye solution for 3 h, only the extracellular matrix is stained. However, if the staining time is increased to 24 h, dye penetration into bacterial cells is observed, resulting in a second photoluminescence maximum during sample analysis. It is important to note that when biofilms are incubated in a dye solution for 3 h, only the extracellular matrix is stained, while with longer staining, penetration of the dye into bacterial cells is observed, and a second photoluminescence maximum appears during sample analysis. The results obtained demonstrate a high potential of using benzimidazole-based compounds as pH-sensitive fluorescent probes operating in a biologically relevant pH range, which can be used for imaging of bacterial biofilms. Full article

1-Butyl-3-methylimidazolium (bmim) ionic liquids (ILs) are widely used for lignocellulose fractionation, yet their role extends beyond mere solvents. This study revealed that bmim-based ILs act as active chemical reagents, modifying the lignin structure in an anion-dependent manner. Thermal treatment (80–150 °C) of spruce dioxane lignin with [bmim]OAc, [bmim]Cl, and [bmim]MeSO₄ resulted in two distinct transformation pathways. In [bmim]MeSO₄, acidic catalysis dominates, leading to lignin condensation (increase in weight-average molecular weight, M_w, to 15.2 kDa at 150 °C) and intense sulfur incorporation (up to 9.9%) via anion-derived methylation/sulfation. Conversely, [bmim]OAc promotes depolymerization (decrease in M_w to 3.6 kDa) and efficient covalent bonding of the bmim cation to lignin (up to 10.8 cations per 100 aromatic units and a 6.5% nitrogen content at 150 °C), preventing condensation. Two-dimensional NMR and HPLC-HRMS analyses revealed the formation of a C–C bond between the C₂ atom of the imidazole ring and the α-carbon of the phenylpropane lignin fragments and allowed for the identification of a number of individual nitrogen-containing lignin oligomers in the [bmim]OAc-treated samples. Their formation likely proceeds via nucleophilic addition of the N-heterocyclic carbene (NHC), derived from the bmim cation by deprotonation with the highly basic acetate anion, to aldehyde groups. The action of [bmim]Cl primarily induces acid-catalyzed transformations of lignin with minimal covalent modification. These findings redefine imidazolium ILs as reactive media in biorefining, where their covalent interactions can influence the properties of lignin but complicate its native structure and the recyclability of the IL. Full article

Non-cephem drugs with 1,3-thiazine-derived rings are very rare, although a number of bioactive 1,3-thiazine derivatives are known. Similarly, 1,4-thiazepine-derived drugs are rare, but many 1,4-thiazepine derivatives show interesting biological activities. Therefore, our aim was the synthesis of such N,S-heterocycles using a versatile and short (1–3 steps) literature method. First, a three-component reaction of a cycloalkene, a thioamide, and an aldehyde provided 5,6-dihydro-4H-1,3-thiazines. Afterwards, Staudinger ketene–imine cycloaddition with chloroketene resulted in β-lactam-fused 1,3-thiazinanes. Finally, treatment with sodium methoxide induced ring expansion, yielding 4,5,6,7-tetrahydro-1,4-thiazepines. This synthetic pathway generates 3–5 new chiral centers with the help of pericyclic reactions, and almost every cycloaddition proceeded in a diastereoselective manner. Two-dimensional NOESY as well as single-crystal X-ray diffraction enabled unequivocal determination of the stereochemistry of all synthesized compounds. Full article