Search Results (123)

Imprinted proteins (IPs) are promising materials for producing artificial alternatives to natural recognition systems (antibodies, aptamers, etc.) due to their high sorption properties and specificity. However, contemporary understanding of the imprinting process at the atomic level is rather limited, which hinders the rational design of more efficient IPs. In this paper, we use computational modeling to provide a description of fundamental principles of protein imprinting at the atomic level. We have modeled several potential associates between the protein matrix and template molecules that form during the imprinting process up to the addition of the cross-linking agent. We used bovine serum albumin (BSA) as the protein matrix and 4-hydroxycoumarin (4–HC) as a molecular template. In combination with computational modeling, extensive experimental analyses including isothermal titration calorimetry (ITC) and NMR spectroscopic methods (¹H NMR and diffusion-ordered NMR spectroscopy (DOSY)) were used to evaluate the potential efficiency of imprinted BSA. This study represents a step toward the future rational in silico design of IPs. Full article

The present study provides an exhaustive exploration of twelve macroalgal species from the Adriatic Sea, including seven brown algae (Ericaria amentacea, Fucus virsoides, Cutleria multifida, Cystoseira compressa, Cystoseira corniculata, Gongolaria barbata and Padina pavonica), three green algae (Codium adhaerens, Codium vermilara and Ulva lactuca), and two red algae (Scinaia furcellata and Asparagopsis taxiformis). Matrix solid-phase dispersion (MSPD) was applied as the extraction technique, using generally recognized as safe (GRAS) solvents. The bioactive profile of the extracts was assessed through the quantification of total phenolic content (TPC) and antioxidant activity. Among the three phyla, U. lactuca, F. virsoides and S. furcellata exhibited the highest TPC (0.8, 26 and 3.0 mgGAE·g⁻¹) and antioxidant activity (1.9, 38 and 7.5 mgTE·g⁻¹), respectively. Targeted HPLC-MS/MS analysis enabled the identification of nineteen phenolic compounds across all taxa. Chlorophyta showed a characteristic profile enriched in coumarins, benzaldehydes and flavanones, including the selective detection of 7-hydroxycoumarin in species with higher antioxidant potential. Additionally, compounds such as chlorogenic, rosmarinic and caffeic acids exhibited taxon-specific distributions that may explain differences in antioxidant activity. Complementary untargeted ultra-high performance liquid chromatography quadrupole time-of-flight (UHPLC-QToF) metabolomics analysis provided broader coverage, revealing eighty metabolites spanning phenolics, sugars, organic acids, lipids, amino acids and their derivatives. Notably, the proposed detection of fatty acid esters of hydroxy fatty acids (FAHFAs) represents the first report of these compounds in macroalgae, alongside a pronounced presence of sulphated phenolics. Overall, these findings provide a robust baseline on the bioactivity and chemical composition of Adriatic macroalgae, highlighting their value as a natural source of functional compounds. Full article

Coumarin-based compounds are recognized for their chemical versatility and diverse biological activities, yet clinical applications remain largely confined to 4-hydroxycoumarin anticoagulants. To bridge this translational gap, coumarin scaffolds have been increasingly employed in prodrug design to enable controlled activation, targeted delivery, and theranostic functionality. This review critically evaluates whether coumarin-based prodrugs fulfill their therapeutic promise or remain primarily preclinical tools across oncology, inflammation, infectious diseases, and cardiovascular disorders. Strategies including enzymatic-, pH-, redox-, and light-triggered activation, as well as subcellular targeting and multifunctional hybrids, are discussed. Preclinical studies demonstrate improved bioavailability, reduced off-target toxicity, and real-time fluorescence monitoring, yet most compounds remain at the in vitro or small-animal model stage. Despite their mechanistic and conceptual potential, clinical translation is constrained by molecular complexity, pharmacokinetics, safety, and regulatory challenges. Overall, coumarins constitute a versatile multifunctional platform whose therapeutic impact relies on rigorous in vivo validation and strategic optimization. Full article

Oxidative stress seems to be part of many deranged processes in the organism, affecting multiple degenerative conditions at a cellular and tissue level. Coumarins and flavonoids comprise two main categories of naturally derived compounds with multiple effects and applications. Our aim in this paper is the design of compounds with increased antioxidant activity with the conjugation of two moieties with highly antioxidant potency in the frame of one molecule. A series of novel derivatives, comprising fusion of 7-hydroxycoumarin (Umbelliferone) and Quercetin (flavonol) have been synthesized using classical organic chemistry methods. Additionally, one novel flavone derivative was prepared for comparison. The novel compounds were tested for their radical, reactive oxygen and nitrogen species (ROS and RNS) scavenging, their reductive activity, and their labile metal chelating potency, as well as with in silico tools. All of them were more active, in most cases, than reference molecules Trolox and vitamin C. The most active compound 2 reached IC₅₀ of 4.03 and 43.75 μM for ABTS and DPPH, respectively (up to three times lower than that of Trolox). Compound 1 was of equal to vitamin C activity in H₂O₂ scavenging, whilst compound 3 was up to 6.4 times more active than Trolox in NO scavenging. Since our designed compounds seem to exhibit high antioxidant potential, scavenging reactive nitrogen and oxygen species, which are accumulated and promote the progression of inflammatory conditions, and have reductive and metal chelating abilities, they can be considered as potential candidates for protection in cases of oxidative stress derived toxicity. Full article

The separation of rare earth elements (REEs) with similar chemical properties remains a relevant challenge today, most often addressed using liquid–liquid and solid-phase extraction with various chelating agents. Excellent complexing agents for REEs are 1,3-diketones and their analogs. We have for the first time proposed a method for preparing a material consisting of a covalently immobilized 3-acyl-4-hydroxycoumarin ligand on silica. For its synthesis, we employed a strategy based on the “click” reaction of 3-azidopropyl silica with a propargyl-containing coumarin–chalcone conjugate—this approach is the most tolerant and does not affect the coordinationally active fragment of the ligand. The material was characterized by thermal analysis, IR spectroscopy, and ¹³C NMR. The potential of the synthesized material for REE preconcentration was demonstrated at pH 5–5.5: high extraction efficiency for Gd(III), Dy(III), Er(III), Eu(III), Sm(III), and Yb(III) was observed, with fast adsorption kinetics (30 min) and extraction degrees of ~98%. Under unified conditions of static and dynamic extraction for Gd(III), Dy(III), Er(III), Eu(III), Sm(III), and Yb(III), affinity series toward the surface were obtained as a function of the distribution coefficient. It was shown that 10-fold molar excesses of Fe(III), Al(III), Cu(II), Ni(II), and Co(II) allow retention of more than 95% extraction for Dy(III) and Er(III). After adsorption of Dy(III) and Er(III), shifts in the carbonyl group absorption bands are visible in the IR spectra of the material, indicating a chelating mechanism of sorption. Additional studies are required for implementation in analytical and preparative REE separation schemes; however, preliminary data show that the material is a highly active adsorbent. Full article

Rapid, sensitive, and environmentally sustainable spectrophotometric methods for the determination of nitrite (${{\mathrm{N}\mathrm{O}}_2}^{-}$) in environmental specimens are proposed. The presented procedures are grounded in the diazotization of sulphathiazole (STZ), followed by coupling with rhodanine (RDN) or 7-hydroxycoumarin (7-HC) in an alkaline medium, and the results were studied. This reaction gave an intense soluble red color at 504 nm and a pale red color at 525 nm for RDN and 7-HC, respectively. The conditions producing the maximum performance and other important analytical criteria in relation to the proposed procedures were investigated to enhance their sensitivity. Beer’s law was abided by for ${{\mathrm{N}\mathrm{O}}_2}^{-}$ over the concentration ranges of 0.08–2.0 µg mL⁻¹ and 0.04–2.4 µg mL⁻¹ using RDN and 7-HC, respectively. The lower limit of detection (LLOD), lower limit of quantification (LLOQ), molar absorptivity (ε), and Sandell’s sensitivity were calculated as follows: 0.0303 µg mL⁻¹, 0.0918 µg mL⁻¹, 4.20 × 10⁴ L mol⁻¹ cm⁻¹, and 1.63 × 10⁻⁶ µg cm⁻² (in the case of RDN); and 0.0387 µg mL⁻¹, 0.1172 µg mL⁻¹, 6.90 × 10⁴ L mol⁻¹ cm⁻¹, and 1.00 × 10⁻⁶ µg cm⁻² (in case of 7-HC). Furthermore, the ecological implications were assessed using three green assessment methodologies: Analytical Eco-Scale (ESA), Analytical GREEnness metric (AGREE), and Green Analytical Procedure Index (GAPI). Thus, our proposed procedures are fully validated and implemented in order to carry out ${{\mathrm{N}\mathrm{O}}_2}^{-}$ quantification in the selected ecological samples (water and soil samples). Full article

7-hydroxycoumarin-4-acetic acid has been synthesized via Pechman condensation. In silico evaluation 7-hydroxycoumarin-4-acetic acid as a ligand of different structures of CYPs from PDB database was completed. The results of docking reveal possibilities to use this compound as a cytochromes P450 substrate. The best energy binding amongst CYPs database was found for human CYP1A1 structure. Our results provide certain opportunities to use coumarin derivatives as inhibitors or activators of CYPs. Full article

In this work, biscoumarin molecules were obtained by a multicomponent reaction, without catalysts, under thermal heating or microwave irradiation. First, optimization tests were performed using benzaldehyde and 4-hydroxycoumarin as starting substrates. The optimal temperature (100 °C), solvent (1-propanol), and reaction time (4 h for conventional heating and 1 h for microwave irradiation) were then employed for the reaction between 4-hydroxycoumarin and different 3-formylchromones to obtain biscoumarins. Good yields and selectivity, which in most cases were greater than 65%, both with conventional thermal heating and microwave radiation, were achieved. Full article

The invasive plant Heracleum sosnowskyi Manden. is a valuable source of a number of bioactive metabolites that can be used in the pharmaceutical industry and medicine and may have some other applications as well. Today, there is a need to summarize data on these substances as well as analyze the toxicological profile of the metabolites of H. sosnowskyi. In this study, we collected a dataset of 225 metabolites of H. sosnowskyi from different literature sources and performed cluster analysis of their chemical structures; we revealed five main clusters of compounds: terpenoids, aromatic compounds, polyaromatic compounds, fatty acids, and furanocoumarins. In order to fill the gaps in the experimental data on the toxicity of the studied substances, we used machine learning (ML) algorithms previously designed for high-accuracy prediction of toxicity end-points. The ML-based approach allowed us to fill in up to 90% of the missing median lethal dose $L{D}_{50}$ (mouse) data for the studied molecules. The validity of each predicted value was confirmed by analyzing the applicability domain of the used ML models. For the calculations and ML modeling, we used the Syntelly chemoinformatics platform. For the most toxic compounds—hydroxycoumarins and furanocoumarins of H. sosnowskyi—the values for hepatotoxicity, drug-induced liver injury (DILI), cardiotoxicity, and carcinogenicity were predicted. Based on the analysis of $L{D}_{50}$ values for the mouse animal model, the greatest toxicity for furanocoumarins is expected with the intravenous route of administration (62–450 mg/kg), which can cause drug-induced liver injury. At the same time, the data do not show high cardiotoxicity risks for the studied furanocoumarins. Based on the presented results, we discuss prospects of using some of the compounds as pharmaceutical agents. Full article

Tomato leaves, typically discarded during harvest, are a rich yet underutilized source of bioactive compounds. This study aimed to valorize tomato leaves by optimizing the extraction of their phenolic compounds using a water-based method and response surface methodology. The optimal conditions, notably heating a mixture of 1:50 solid-to-liquid ratio at 71 °C for 29 min, yielded the most total phenolic content and antioxidant activity. The biological activities of the lyophilized tomato leaf extract (TLE) were then assessed. TLE showed dose-dependent antimicrobial activity against Escherichia coli and Candida albicans, but neither against Pseudomonas aeruginosa nor Staphylococcus aureus. In addition, it demonstrated moderate cytotoxicity against MCF-7 breast cancer cells with an IC₅₀ value of 114.5 µg/mL. Interestingly, the extract significantly reduced intracellular reactive oxygen species levels in RAW 264.7 macrophages, supporting its anti-inflammatory potential. LC-MS analysis identified rutin (45.21%), 4-hydroxycoumarin (13.60%), and α-tomatine (12.37%) as the major chemical constituents in TLE, suggesting contributing effects behind the observed bioactivities. These results support the potential of tomato leaf extract as an eco-friendly source for functional ingredients, transforming agricultural waste through green extraction into valuable applications for nutraceuticals and sustainable product development. Full article

Bamboo shoot boiled liquid (BSBL), a processing byproduct containing soluble proteins, peptides, amino acids, carbohydrates, and phenolics, is typically discarded, causing resource waste and environmental issues. This study analyzed metabolic changes in BSBL during Pediococcus pentosaceus B49 fermentation. The result of partial least squares discriminant analysis (PLS-DA) revealed significant metabolite profile differences across fermentation times (0 h, 24 h, 48 h, 72 h, 96 h). The most substantial alterations occurred within the first 24 h, followed by stabilization. Compared to unfermented BSBL, fermented samples exhibited significantly elevated signal intensities for 5,7-dimethoxyflavone, cinnamic acid, 3,4-dihydro-2H-1-benzopyran-2-one, 6,8-dimethyl-4-hydroxycoumarin, and 2-hydroxycinnamic acid (p < 0.05), showing upward trends over time. Conversely, (+)-gallocatechin intensity decreased gradually. Bitter peptides, such as alanylisoleucine, isoleucylisoleucine, leucylvaline, and phenylalanylisoleucine, in BSBL exhibited a significant reduction following fermentation with P. pentosaceus B49 (p < 0.05). KEGG enrichment indicated tyrosine metabolism (ko00350) and arginine/proline metabolism (ko00330) as the most impacted pathways. These findings elucidate metabolic regulation in BSBL fermentation, supporting development of functional fermented bamboo products. Full article

The search for substances that increase the immunity of bees is becoming a necessity in the era of various environmental threats and the declining immunocompetence of these insects. Therefore, we tested the biological and physicochemical properties of 7-diethylamino-4-hydroxycoumarin (7DOC). In a cage test, two groups of bees were created: a control group fed with sugar syrup and an experimental group fed with sugar syrup with the addition of 7DOC. In each group, the longevity of the bees was determined and the protein concentrations and antioxidant activities in the bees’ hemolymph were determined. The bees fed with 7DOC lived 2.7 times longer than those in the control group. The protein concentrations and activities of SOD, CAT, GPx and GST, as well as the TAC levels, were significantly higher in the hemolymph of the supplemented workers. To confirm these potent biological properties of 7DOC, the UV-Vis spectra, emission and excitation of fluorescence, synchronous spectra and finally the fluorescence lifetimes of this compound were measured using the time-correlated single photon counting method, in various environments differing in polarity and in the environment applied in bee research. This compound was shown to be sensitive to changes in solvent polarity. The spectroscopic assays were complemented with crystallographic tests of the obtained monocrystals of the aforementioned compounds, which attested to the aggregation effects observed in the spectra measurements for the selected coumarin. The research results confirm that this compound has the potential to be implemented in apiary management, which will be our application goal, but further research into apiary conditions is required. Full article

This study developed a rapid, non-destructive method combining near-infrared (NIR) spectroscopy with chemometric techniques (OPLS-DA, ANN, and PLS) to accurately identify the geographic origin and quantify six key chemical components of V. thibetica rhizomes. The results demonstrated that the combination of NIR spectroscopy, OPLS-DA, and ANN successfully and accurately distinguished V. thibetica from three distinct origins. Additionally, combining partial least squares (PLS) and NIR spectroscopy, the contents of chlorogenic acid, isochlorogenic acid A, isochlorogenic acid C, umbelliferone (7-hydroxycoumarin), senkyunolide I, and ligustilide measured by HPLC-UV were used as reference values to predict the contents of the six chemical components in V. thibetica, and spectral preprocessing methods optimized the model. The correlation coefficients of the final quantitative model for the contents of the six components in V. thibetica were between 0.7852 and 0.9538, the root mean square error of calibration (RMSEC) was between 0.0027 and 0.2530, and the root mean square error of prediction (RMSEP) was between 0.0031 and 0.4240. The results suggest that NIR spectroscopy combined with OPLS-DA and ANN can be used as a rapid and accurate method to evaluate the quality of V. thibetica herbs. Full article

Chronic pain significantly impacts quality of life and is often accompanied by inflammation, a natural bodily response that can become harmful when excessive. The orofacial region is commonly affected, making effective treatment crucial. However, current drugs often cause undesirable side effects, highlighting the need for new pharmacological alternatives. 4-hydroxycoumarin (4-HC), a natural compound, has shown promising antinociceptive and anti-inflammatory effects, but studies confirming its specific properties are limited. In silico analyses suggest that 4-HC exhibits favorable pharmacokinetic characteristics, not interacting with P-glycoprotein and successfully crossing the blood–brain barrier. Molecular docking studies indicate that its effects may be mediated through NMDA_R or by inhibiting iNOS. Our study assessed the antinociceptive and anti-inflammatory effects of 4-HC in animal models at doses of 25, 50, and 75 mg/kg. 4-HC significantly reduced abdominal contortions induced by acetic acid and decreased nociceptive rubbing in orofacial pain models induced by formalin, glutamate, and capsaicin. Interactions with opioid receptors were not observed, suggesting that 4-HC’s antinociceptive effect does not involve this pathway. Additionally, 4-HC reduced paw edema induced by carrageenan and significantly decreased leukocyte migration and TNF-α levels. These findings highlight the therapeutic potential of 4-HC and warrant further investigation into its mechanisms. Full article

Multi-target-directed ligands (MTDLs) represent a promising frontier in tackling the complexity of multifactorial pathologies like Alzheimer’s disease (AD). The synergistic inhibition of MAO-B, MAO-A, and AChE is believed to enhance treatment efficacy. A novel coumarin-based molecule substituted with O-phenylpiperazine via three- and four-carbon linkers at the 5- and 7-positions, has been identified as an effective MTDL against AD. Employing a medicinal chemistry approach, combined with molecular docking, molecular dynamic simulation, and ΔG_bind estimation, two series of derivatives emerged as potent MTDLs: 8-acetyl-7-hydroxy-4-methylcoumarin (IC₅₀: 1.52–4.95 μM for hAChE, 6.97–7.65 μM for hMAO-A) and 4,7-dimethyl-5-hydroxycoumarin (IC₅₀: 1.88–4.76 μM for hMAO-B). They displayed binding free energy (ΔG_bind) of −76.32 kcal/mol (11) and −70.12 kcal/mol (12) against AChE and −66.27 kcal/mol (11) and −62.89 kcal/mol (12) against MAO-A. It is noteworthy that compounds 11 and 12 demonstrated efficient binding to both AChE and MAO-A, while compounds 3 and 10 significantly reduced MAO-B and AChE aggregation in vitro. These findings provide structural templates for the development of dual MAO and AChE inhibitors for the treatment of neurodegenerative diseases. Full article