In this study, the phenolic compound profiles and bioactivity properties of aerial part extracts obtained from Stachys annua, Stachys cretica, and the endemic species Stachys tmolea, all of which are recognized as medicinal plants in Türkiye, were investigated. In this context, phenolic components in the flavonoid-subgroup extracts like flavanones, flavonols, flavan-3-ols, flavan‑3- ols acid hydrolysis, flavones, and in the phenolic acids and their liquid-solid phase acid-base hydrolysis extracts were determined by reversed-phase high-performance liquid chromatography coupled with a diode array detector (RP-HPLC-DAD). Also, the total-phenolic, total-flavonoid, and total-tannin contents of the Stachys species were estimated. Among the evaluated antioxidant capacities of the flavonoid and phenolic acid extracts, S. annua exhibited the strongest scavenging capacities against 2,2-diphenyl-1-picrylhydrazyl and hydroxyl-radicals with half-maximal inhibitory concentration (IC50) values of 5.53 ± 0.32 and 1.09 ± 0.02 μg mL-1, respectively. S. tmolea indicated the highest nitric-oxide radical scavenging and metal-chelating capacities. The highest enzyme inhibitory activities were determined in S. annua for acetylcholinesterase and in S. cretica for tyrosinase. The phenolic acid extracts displayed moderate cytotoxic activity against ACC-201, OE-33, HeLa, and HepG2 cells with IC50 values ranging from 20.1 ± 1.25 to 45.3 ± 1.35 μg mL-1. The results show that the phenolic composition and bioactivity properties of investigated Stachys species are potentially promising for applicability in the food and pharmaceutical industries.
Anticancer activity of the 7-hydroxycoumarin N(3)-substituted thiosemicarbazones was evaluated against the human prostate cancer (DU145) and human embryonic kidney‑derived HEK293 cell lines. The cytotoxicity of the free ligands (HL1-HL4) along with the copper complexes [Cu(L1)Cl]-[Cu(L4)Cl] were checked using 3-(4,5-dimethylthiazol-2-yl)-2,5‑diphenyltetrazolium bromide (MTT) assay. The most potent compound, [Cu(L1)Cl], induced cell death of 56.25 ± 1.17, 73.30 ± 0.71, and 82.33 ± 0.47% at concentrations of 10, 50 and 100 μM, respectively. Cell viability assays revealed that [Cu(L1)Cl] suppressed cancer cell proliferation in a dose-dependent manner with minimal cytotoxic toward HEK293 cells. Acridine Orange/Ethidium Bromide (AO/EB) staining of the compound [Cu(L1)Cl] demonstrated apoptotic morphological changes in DU145 cells, including nuclear shrinkage and chromatin condensation. The intracellular reactive oxygen species (ROS) generation induced by the compound [Cu(L1)Cl] in DU145 cells was evaluated using the 2’,7’-dichlorofluorescein diacetate (DCFH-DA) fluorescent probe. The results showed a significant elevation in ROS levels compared with the untreated control group, with ROS production increasing in a concentrationdependent manner. Additionally, molecular docking analyses revealed that ligands HL1-HL4 and their copper(II) complexes were particularly effective in inhibiting the epidermal growth factor receptor (EGFR) protein.
The Amazon hosts countless plant species, many still unknown to science. Among catalogued species, hundreds are edible, yet most are rarely consumed or locally restricted. Known in Brazil as PANCs ("Plantas Aliment & iacute;cias N & atilde;o Convencionais"), these unconventional food plants, these species can enhance food security, especially for vulnerable populations. Beyond nutrition, studies reveal their nutraceutical potential due to specialized metabolites such as polyphenols, terpenes, and alkaloids, which enable applications in supplements, cosmetics, and herbal formulations. In this context, Theobroma mariae (Mart.) K. Schum., or "cacau-jacar & eacute;", is a little-known fruit-bearing plant with promising applicability. This study annotated its volatile and non-volatile compounds in pulp and seeds using headspace solid-phase microextraction gas chromatography coupled with mass spectrometry (HS-SPME/GC-MS) and ultra-high-performance liquid chromatography-high resolution tandem mass spectrometry (UHPLC-HRMS/MS), respectively. A total of 72 volatile and 32 non-volatile compounds were annotated. Fatty acids predominated in the pulp volatilome, whereas theacrine was the main volatile compound in the seeds. Phenolic compounds dominated the non-volatile fraction, notably flavonoid-C-glycosides, O-glycosides, and O-glucuronides. The findings highlight T. mariae as a valuable yet underutilized Amazonian fruit, whose chemical profile resembles that of common cacao and offers potential for novel applications in food, nutraceutical, and cosmetic formulations.
N-Bromosuccinimide (NBS) is a versatile brominating reagent. It is used not only in radical bromination but also in electrophilic addition and electrophilic substitution reactions. NBS can be used to obtain aryl bromides, which are useful for further functionalization, such as coupling reactions for C/N/O/S-aryl bond formation. However, the succinimide group of NBS is poorly explored and is often treated as a waste. In this work, it is proposed the full use of NBS, both for bromination of arenes and for the incorporation of the succinimide group in a one-pot fashion. Using low-cost reagents such as Cu2O and K3PO4, N-arylsuccinimides were obtained in moderate to good yields directly from non-halogenated aromatics. It was observed that microwave irradiation was crucial to circumvent the low nucleophilicity of succinimide.
α-Nitroolefins are introduced as novel dipolarophiles in [3 + 2] cycloadditions with organic azides, enabling the regioselective synthesis of 1,4-disubstituted 1,2,3-triazoles under metal-free conditions. The α-nitroolefin is generated in situ from the corresponding nitro alcohol-derived acetate. Reaction optimization identified Brønsted acid catalysis in dimethylformamide (DMF) under microwave irradiation as the optimal conditions, affording triazoles in yields up to 71%. The methodology tolerates a range of aryl-substituted α-nitroolefins and aliphatic azides, although aryl azides exhibit diminished reactivity. Computational studies reveal that the cycloaddition proceeds preferentially through a stepwise mechanism. Regioselectivity arises from a combination of favorable frontier molecular orbital interactions and a lower-distortion energy pathway, in which azide deformation plays a dominant role. These findings provide a mechanistic basis for the exclusive formation of 1,4-triazoles and highlight the impact of nitro group positioning on cycloaddition reactivity.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder for which acetylcholinesterase inhibitors (AChIs) are commonly prescribed to mitigate cognitive decline. In this study, untargeted metabolomics and lipidomics based on liquid chromatography coupled to in plasma samples from AD patients before and during AChI treatment. Differential feature selection and pathway enrichment analyses revealed significant modulation of lipidic and energetic metabolism. Alterations in glycerophospholipid and glycosphingolipid metabolism, accompanied by a progressive reduction in phospholipids, suggest an increased demand for substrates associated with acetylcholine synthesis. Enrichment of carnitine transport and fat-soluble vitamin (E and D) metabolism after AChI treatment points to bioenergetic dysfunction and enhanced oxidative and inflammatory stress in AD. Changes in arginine and proline metabolism, carbohydrate metabolism, and butyrate metabolism further reflect key biochemical disturbances in AD, including glucose hypometabolism and nitrosative stress. These findings provide insights into the systemic metabolic effects of AChI therapy and highlight the potential of LC-HRMS-based metabolomics and lipidomics for biomarker discovery and therapeutic monitoring in AD.
Ocotea odorifera ("canela-sassafras") has a rich history in the traditional medicine of Brazil for treating inflammatory conditions such as edema, arthritis, and fever. Ethnobotanical records indicate that leaves are commonly prepared by decoction to relieve inflammatory conditions. This research applied metabolomics strategies to investigate how seasonal variation influences the chemical composition and anti-inflammatory activity of O. odorifera leaf essential oils (EOs). Leaves were collected monthly over one year, and EOs were extracted via hydrodistillation. Gas chromatographymass spectrometry (GC-MS) was applied for EOs chemical composition identification. The EOs were assessed using an ex vivo anti-inflammatory assay, measuring prostaglandin E-2 (PGE(2)) levels in lipopolysaccharide-stimulated human whole blood. Ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) was employed to determine PGE2 inhibition levels. Untargeted metabolomics demonstrated that EOs harvested in autumn and spring exhibited fluctuations in the chemical composition, which favoured greater PGE2 inhibition levels, with pronounced seasonal shifts among the minor compounds. Orthogonal partial least squares discriminant analysis (PLS-DA) revealed terpinen-4-ol as statistically different and positively correlated with the increase in the anti-inflammatory activity. Safrole, a major compound, demonstrated no relevant seasonal variation. These findings highlight and confirm how seasonal chemical dynamics modulate the specialized metabolism and the anti-inflammatory activity profile of O. odorifera EOs.
Coumarins are versatile heterocyclic scaffolds widely explored for their photophysical properties and applications in fluorescence-based sensing. In this study, a series of C3-functionalized sulfur-substituted 4-hydroxycoumarins 2a-2k was investigated as potential fluorescent probes for metal ion detection. The compounds were comprehensively characterized using spectroscopic techniques, electrochemical analysis, and density functional theory (DFT) calculations. Photophysical studies revealed intense UV absorption and fluorescence emission in the violet region, with moderate Stokes shifts consistent with intramolecular charge transfer (ICT) transitions. Time-resolved measurements indicated nanosecond-scale excited-state lifetimes, while theoretical calculations supported the ICT nature of the electronic transitions. Preliminary aggregation studies demonstrated aggregation-induced emission (AIE) behavior for derivative 2a, suggesting potential applications in solid-state luminescent systems. Among the investigated compounds, derivative 2k exhibited the most promising sensing performance, showing selective fluorescence quenching toward Hg2+ ions through heavy atom effects and ligand-to-metal charge transfer interactions. Quantitative fluorescence titration revealed a Stern-Volmer constant on the order of 104 M–1, with limits of detection and quantification of 3.66 and 11.10 μM, respectively. Furthermore, the probe demonstrated rapid response, good anti-interference capability, and successful detection of Hg2+ in cosmetic samples. These results highlight sulfur-substituted 4-hydroxycoumarins as promising fluorescent platforms for the development of optical sensors for heavy metal monitoring in environmental and consumer products.
Sulfoxonium ylides have emerged as safer alternatives to diazo compounds for generating metal carbenes in X–H insertion reactions. However, most studies still focus on aryl ester ylides and on a relatively narrow selection of noble metal catalysts. In this work, it was investigated aryl, alkyl, and unsubstituted sulfoxonium ylides (ester, keto and amide) in X–H insertion reactions mediated by metal carbenes. A broad range of catalysts was evaluated under standardized conditions, including noble metals such as Au, Ag, Pt, Pd, Rh, Ir, and Ru, and non-noble metals such as Fe, Cu, Zn, Ni, V, Mn, Co, Zr, and Sc. For the aryl ester ylide, several catalysts promoted N–H insertions in good yields, with notable performance from Ir, Rh, Fe, Ag, Sc, and V complexes. For unsubstituted ylides, only Rh, Ir, and Ru complexes delivered satisfactory results. Based on these data, alkyl ylides were evaluated only with Ir, Rh, and Ru, showing high efficiency for Ir and Rh. The aryl keto ylide displayed distinct behavior, forming mainly the imine and 1,2-dicarbonyl products. O–H and S–H insertions were also carried out for the aryl ester ylide using different catalysts, giving yields between 10-94%.
Latent fingerprints (LFPs) are a key tool in forensic identification due to their uniqueness and long-term stability. However, their visualization at crime scenes remains challenging, highlighting the need for more efficient development methods. Recent studies have focused on organic compounds exhibiting aggregation-induced enhanced emission (AIEE), with weak luminescence in solution but strong emission in aggregated states. When incorporated into the sebaceous residues of fingerprints, these compounds can significantly enhance luminescence, enabling high-contrast and well-defined LFP images. In this work, new aryloxy-benzothiadiazole (BTD) derivatives were developed for LFP detection. Two compounds, OcA-BTD and Pyr-BTD, were synthesized, each designed according to a distinct fingerprint recognition strategy. For Pyr-BTD, a pyridine moiety was incorporated to promote interactions between the basic nitrogen and amino acids and fatty acids present in LFP residues. In contrast, OcA-BTD was designed with a highly lipophilic octadecyl chain to enhance affinity toward the lipid-rich components of LFPs. As a result, only the octadecyl-substituted compound exhibited pronounced AIEE, showing green emission in the aggregated state. This AIEEgen enabled the clear visualization of levels 1, 2, and 3 on fingerprint details on different substrates, providing excellent contrast between LFPs ridges and furrows.
Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Computational techniques, such as molecular docking, are essential for drug repurposing and screening to identify potential treatments for the virus. This approach enables the investigation of interactions between a ligand and a key protein. In this study, in silico methods, including molecular docking and molecular dynamics (MD) simulations, were employed to evaluate the antiviral potential of 10 natural curcumins against SARS-CoV-2. Density functional theory (DFT) calculations were also performed to analyze the structural properties of the selected ligands. Our findings suggest that the curcumins demethoxycurcumin, bisdemethoxycurcumin, and cassumunin B are promising inhibitors of the SARS-CoV-2 3CLPro protein.
Toxoplasmosis, caused by the obligate intracellular protozoan Toxoplasma gondii, represents a relevant zoonotic disease affecting both human and animal health. Free-ranging neotropical primates (FRNP) are particularly susceptible to severe clinical outcomes; however, systemic metabolic alterations associated with infection in these species remain poorly characterized. This study aimed to investigate serum metabolic perturbations in FRNP naturally infected with T. gondii using an untargeted liquid chromatography-mass spectrometry (LC-MS) approach integrated with multivariate and machine learning (ML) analyses. Serum samples from infected and non-infected FRNP were analyzed by liquid chromatography-high-resolution mass spectrometry (LC-HRMS), yielding 1025 metabolic features following rigorous data preprocessing and quality control procedures. Both unsupervised and supervised ML models were employed to explore group discrimination. Several metabolic features (m/z 809.2713, 660.5429, 718.3614, 537.5458, 707.2745, 318.2951) were significantly altered in infected performance (area under the curve (AUC) = 0.78; sensitivity = 0.88). Collectively, these findings indicate that T. gondii infection in FRNP is associated with measurable systemic metabolic perturbations. The identified features should be interpreted as preliminary metabolic signatures, warranting further targeted validation and larger-scale studies to clarify their biological and potential translational relevance.
Few studies in the Peruvian Amazon have jointly evaluated soil macrofauna and heavy metal contamination in cacao agroecosystems. This study integrated ICP-MS (inductively coupled plasma mass spectrometer) multielement analysis, soil macrofauna assessment, and multivariate statistics in five cacao plots (113-1,102 m above sea level) under monoculture and diversified management with varying fertilization and pesticide inputs. Twelve elements were quantified in 25 composite soil samples, and macrofauna were collected from 25 soil monoliths (25 cm & times; 25 cm & times; 20 cm), yielding eight taxa. As, Cd, and Pb ranged from 1.74-8.42, 0.139-0.964, and 8.21-53.9 ppm, respectively, with peak concentrations in plot P05. Plot P02, under diversified management, showed the greatest macrofaunal diversity (S = 4.6 (species richness); H = 1.15 (Shannon diversity index). Hymenoptera (1,060 individuals) and Oligochaeta (257 individuals) dominated the community, while Coleoptera, Isopoda, and Blattodea were scarce. Most metal-macrofauna correlations were weak; however, significant positive associations were detected between sulfur and Helicidae (rho = 0.401 (Spearman rank correlation coefficient), p < 0.05) and chromium and Coleoptera (rho = 0.465, p < 0.05). These findings suggest that soil mineral composition and management practices, beyond toxic-metal loads alone, jointly shape macrofaunal structure, underscoring the need for sustainable soil monitoring in the Central Rainforest Region of Peru.
This study explores the application of paper spray ionization-mass spectrometry (PSI-MS/MS) in evaluating the metabolomic profiles of lettuce varieties cultivated under soil-based and hydroponic conditions. Compared to electrospray ionization tandem mass spectrometry (ESI-MS/MS), the PSI-MS/MS technique demonstrated improved sensitivity and robust ion signal intensity, allowing effective discrimination between the chemical constituents of the lettuce samples. Significant metabolic differences were identified between the cultivation methods, particularly in the negative ionization mode. PSI-MS/MS provided detailed insights into the chemical composition due to its high sensitivity and minimal sample preparation requirements. The study further analyzed three lettuce varieties (loose leaf, iceberg, and oak leaf) using PSI-MS/MS, revealing distinct ion profiles and variation in ion abundances. Chemometric techniques, including parallel factor analysis (PARAFAC) and partial least squares for discriminant analysis (PLS-DA) with variable selection were utilized to differentiate between lettuce varieties and cultivation methods. This approach highlighted the impact of growing conditions on the metabolic composition of lettuce, identifying key ions such as choline, mannose, and malic acid as significant markers. Overall, the integration of PSI-MS/MS with chemometric tools provides a comprehensive approach for metabolomic profiling, offering valuable insights into the effects of cultivation methods on the nutritional and chemical properties of lettuce. This study underscores the potential of PSI-MS/MS in agricultural and food science research, contributing to the optimization of cultivation practices and the enhancement of crop quality, while also adhering to the principles of green analytical chemistry.
Late-stage functionalization (LSF) has emerged as a powerful strategy for the direct modification of structurally complex molecules, enabling rapid access to valuable analogues and offering a step- and resource-economical platform for molecular diversification. Transitionmetal catalysis has played a central role in advancing these transformations. However, to date, late-stage metal-catalyzed C–H functionalization has relied predominantly on noble transition metals. First-row (3d) transition metals are more abundant, less expensive, and generally less toxic, making them attractive alternative for sustainable LSF applications. In addition, they offer complementary reactivity to their noble metal congeners. This review focuses in the intersection of 3d-metal catalysis, C–H activation, and late-stage functionalization, with particular emphasis on the modifications of aromatic systems in complex molecules. A critical analysis of the key challenges associated with the use of 3d metals in these transformations, including issues related to catalyst reactivity and stability, as well as the chemo- and regio-selectivity is provided. By examining the advancements and limitations over the past decade, this review aims to offer insights into emerging strategies to overcome these challenges and to guide the development of more efficient and sustainable methodologies in transition-metal catalyzed C–H functionalization.
