Search Results (934)

The chemical composition and bioactivities of dry methanol extracts from roots, leaves and fruits of Prangos trifida (Apiaceae), collected in Serbia, were investigated. LC-DAD-QTOF-MS/MS analysis revealed 30 compounds, primarily polyphenols and coumarins. The root and leaf extracts were rich in chlorogenic and/or 3,5-di-O-caffeoylquinic acid (18.20–26.14 mg/g extract), and the fruit extract in oxypeucedanin hydrate and prantschimgin (46.50 and 71.64 mg/g). The leaf extract exhibited the highest total phenolic content (62.86 mg quercetin equivalents/g), total antioxidant activity (FRAP = 0.71 mmol Fe²⁺/g) and DPPH radical scavenging ability (44.08 mg quercetin equivalents/g). Antimicrobial activity testing (11 bacteria and three yeasts, microdilution method) showed that the most active were the root and leaf extracts against Micrococcus luteus, Staphylococcus aureus, S. epidermidis and Candida albicans (MIC = 0.625–5 mg/mL). The fruit extract showed the strongest cytotoxicity against tested stomach, colon and hypopharynx cancer cell lines (MTT test), with the highest selectivity toward hypopharynx cancer FaDu cells (selectivity index 4.71; determined in relation to non-cancerous VERO cells). No antiviral activity against herpesvirus type 1 was found. The results indicate that P. trifida represents a promising source of polyphenols and coumarins, notably expanding current knowledge on its chemical composition and supporting its potential relevance for pharmaceutical and food industry applications. Full article

Sonchus asper (L.) Hill is a widely distributed plant traditionally used as both a food source and a medicinal herb. In recent years, increasing interest in natural, safe, and effective cosmetic ingredients has highlighted the potential of plant-derived bioactive compounds. This review provides an overview of the biological properties of S. asper, with particular emphasis on its relevance in cosmetic applications. The plant is characterized by a rich profile of primary and secondary metabolites, including amino acids, fatty acids, vitamins, phenolic acids, flavonoids, coumarins, and terpenoids. These compounds contribute to a broad spectrum of biological activities, such as strong free radical scavenging activity, modulation of inflammatory pathways, and inhibition of the growth of selected skin-associated pathogens, suggesting its potential as a multifunctional cosmetic ingredient. Full article

No data to date are available on the underlying mechanisms by which coumarin (COU) alleviates plant aluminum (Al) toxicity. Citrus grandis (L.) Osbeck seedlings were submitted to 0 (Al0) or 1.2 (Al1.2 or Al³⁺ toxicity) mM AlCl₃·6H₂O and 0 (COU0) or 50 (COU50) μM COU for 18 weeks. The results demonstrated that COU50 attenuated Al1.2-induced decreases of seedling growth, chlorophyll (Chl) level, and CO₂ assimilation (A_CO2) and impairment of the photosynthetic electron transport chain (PETC). Further analysis suggested that reduced tissue Al concentration and enhanced capability to maintain nutrient and redox homeostasis played a role in COU-mediated amelioration of seedling growth inhibition, leaf Chl and A_CO2 decline, and PETC impairment. Notably, seedlings treated with COU0 showed some adaptive responses to Al1.2. For example, Al1.2 decreased the biosynthesis and accumulation of proteins and amino acids to meet the increased need for energy; increased the diphenylpicrylhydrazyl (DPPH) scavenging activity and phenolic compound accumulation to meet the elevated demand for reactive oxygen species (ROS) and Al detoxification; and increased the accumulation of soluble sugars (glucose, fructose, and sucrose) to meet the augmented demand for ROS scavenging and energy. To conclude, the research revealed some mechanisms for COU-mediated amelioration of plant Al³⁺ toxicity. Full article

The increasing resistance of mosquito vectors to synthetic insecticides poses a major challenge to vector control and global public health, underscoring the urgent need for sustainable, environmentally safe alternatives. This study evaluated the larvicidal activity of aqueous, ethanolic, methanolic, and hydroethanolic extracts of Calotropis procera (Aiton) W.T.Aiton leaves against Aedes aegypti larvae. Significant variations in activity were observed across extraction solvent, ecological zone, and harvest season, with hydroethanolic extracts—particularly those collected in Kombissiri during the dry season—exhibiting the lowest LC₅₀ values among the tested extracts (LC₅₀ < 1600 ppm), indicating moderate larvicidal activity. Phytochemical profiling by high-performance thin-layer chromatography (HPTLC) revealed the presence of several classes of secondary metabolites, including flavonoids, phenolic compounds, tannins, sterols/triterpenes, saponins, coumarins, alkaloids, and cardenolides. Correlation analysis revealed strong negative correlations between larvicidal activity and the concentrations of flavonoids and phenolic compounds, suggesting that higher levels of these metabolites are associated with increased larvicidal effectiveness and may contribute to the observed bioactivity, although these associations remain correlative and do not establish direct causality. These findings highlight the potential of C. procera as a source of plant-based larvicides and demonstrate the influence of environmental factors on their efficacy. From an environmental health perspective, such plant-derived solutions could provide preliminary data for the future optimization of sustainable vector control strategies, while reducing ecological impact and reliance on synthetic insecticides. Full article

In this work, three 3-carboxamidecoumarin derivatives (3b, 3c, and 4) were synthesized and characterized by NMR, IR, and single-crystal X-ray. All compounds maintain an essentially planar coumarin scaffold stabilized by an intramolecular N–H⋯O hydrogen bond (S(6) motif), though compound 4 exhibits a more complex bifurcated S₃²(11)[S(6)S(6)S(5)] network that enhances its conformational rigidity. The crystal packing analysis reveals that while all derivatives form one-dimensional (1D) supramolecular tapes through C–H⋯O interactions, their 3D architectures differ significantly: 3b and 3c rely on a diverse combination of π⋯π stacking and lone pair⋯π contacts, whereas 4 is governed by highly directional stacking between the pyran and pyridine rings. Hirshfeld surface analysis and CE-B3LYP energy framework calculations quantified the balance between intermolecular forces, showing that 3b is dispersion-dominated (H⋯H, 43.5%), while 3c achieves a balanced electrostatic–dispersion regime due to the nitro group, which increases O⋯H/H⋯O contacts to 37.1% and yields the highest stabilization energy (−69.1 kJ/mol). These results demonstrate that the electronic nature of the substituents at the 3- and 6-positions drastically modulates the hierarchy of non-covalent interactions, providing key insights for the crystal engineering of coumarin-based supramolecular systems. Full article

Quinazolinone derivatives are well-known anticancer agents; anticancer properties are also part of the broad spectrum of biological activity of coumarins. Conjugates containing quinazolin-4(3H)-one and coumarin fragments linked by polymethylene bridges of varying lengths were designed to improve properties of both parental compounds and create new anticancer or antibacterial agents. 3-{3-[(4-Methyl-2-oxo-2H-chromen-7-yl)oxy]propyl}quinazolin-4(3H)-one was synthesized as the base compound. It demonstrated moderate cytotoxicity against leukemia (K562 and HL60) and neuroblastoma (SH-SY5Y) cells in vitro, combined with relatively low acute, subacute, and chronic toxicity in vivo. Conjugates with various substituents and linkers were then synthesized to evaluate the structure–activity relationship. A study of the synthesized compounds on cell cultures showed that the introduction of a methyl substituent into the benzene ring of the coumarin fragment led to both an increase in cytotoxicity and expansion of its spectrum of action. Testing of the hybrids against Gram-positive and Gram-negative bacteria revealed that the introduction of halogens into the quinazoline fragment in the compounds or the elongation of the linker led to the emergence of pronounced antibacterial properties, which were most clearly manifested against Acinetobacter baumanii. The possibility of directing activity of quinazoline-4(3H)-one–coumarin hybrids by varying the substituents and the length of the linker was shown. Full article

A series of coumarin–amino acid hybrids of glycine, γ-aminobutyric acid, and L-glutamic acid was developed. These compounds were evaluated for their antioxidant and anti-inflammatory activities in vitro and for their drug-likeness in silico. Antioxidant activity was assessed in vitro using the AAPH-induced linoleic acid peroxidation assay. Soybean lipoxygenase and ovine cyclooxygenase 2 were used in vitro to test the inhibitory activity of the adducts. An in silico evaluation was performed using the open-access platforms Molinspiration, SwissADME, PreADMET, Molsoft, GLORYx, CypRules, and LiverTox Workspace. The synthesis of the compounds proceeded via a facile procedure through the corresponding acid in very good yields. The antioxidant activity of the compounds is shown to be highly dependent on the linkage used, with compound 15 presenting the highest activity (93% inhibition). The most active LOX inhibitor is compound 4 (IC₅₀ = 58 μM), while compounds 4 and 5 are the most potent COX-2 inhibitors (IC₅₀ = 55 μM for both). Compounds 4, 9, and 15 are depicted as pleiotropic molecules (compound 4: IC₅₀ for SLOX-1 = 58 μM and IC₅₀ for COX-2 = 55 μM; compound 9: IC₅₀ for COX-2 = 60 μM, and 59% antilipid peroxidation; compound 15: IC₅₀ for COX-2 = 70.5 μM, 93% antilipid peroxidation). An in silico evaluation showed favorable properties of the designed agents, which were quantified, with all the compounds showing a QED score higher than 0.5. The overall results highlight that compound 4 can be used as a lead molecule for the design of more potent agents with a pleiotropic profile. Full article

The persistence of an immunosuppressive microenvironment remains a formidable challenge for cancer immunotherapy, particularly in tumors with immune-excluded or immune-desert phenotypes. Increasing evidence indicates that chronic inflammation and tumor progression are intrinsically linked through shared signaling hubs, including NF-κB and PI3K/Akt. Osthole, a natural coumarin compound, has been reported to exhibit both potent anti-inflammatory and antitumor activities; however, whether these effects reflect a coordinated regulation of the inflammation–cancer axis remains unclear. In this study, we deployed an integrative framework founded on network pharmacology, molecular docking, and rigorous molecular dynamics simulations, complemented by literature-based evidence synthesis, to computationally explore the potential mechanisms underlying Osthole’s dual activities. Our analysis revealed that Osthole’s predicted targets are significantly enriched in signaling pathways bridging inflammatory and oncogenic processes, most notably the PI3K/Akt, NF-κB, and TGF-β/Smad pathways. Crucially, MD simulations provided supportive computational evidence, suggesting that Osthole forms stable, energetically favorable complexes with core protein hubs (AKT1, RELA, and TGFB1) under the simulated conditions. Evidence from representative inflammatory and tumor models supports the biological plausibility of these predictions, including suppression of pro-inflammatory signaling, mitigation of maladaptive tissue remodeling, and induction of apoptosis. Furthermore, in hepatocellular carcinoma models, Osthole-mediated apoptosis appeared linked to HMGB1-related inflammatory signaling, highlighting its potential to modulate the local immune niche. Collectively, this convergence of systems-level predictions and dynamic structural evidence identifies Osthole as a promising multi-target candidate for the coordinated regulation of inflammation-associated tumor progression, providing a robust rationale for further experimental validation. Full article

Endophytic fungi are promising sources of novel antiviral compounds, and the crude extract from Alternaria alternata PO4PR2 has previously shown anti-HIV-1 activity. This study evaluated its efficacy against integrase strand-transfer inhibitor (INSTI)-resistant HIV-1 and its mechanism of action. Key resistance mutations (Y143H, G118R, N155H, and R263K) were introduced into the HIV-1 pNL4.3 clone via site-directed mutagenesis and confirmed through Sanger sequencing. Viral infectivity was assessed in TZM-bl cells, while cytotoxicity was measured using an MTT assay. Antiviral activity was determined through a luciferase-based assay, and integration inhibition was evaluated using integrase activity assays and Alu-gag nested PCR. The extract demonstrated potent inhibition of resistant mutants, with low IC₅₀ values (0.02971–0.1652 μg/mL), and showed minimal cytotoxicity (CC₅₀ = 300 μg/mL), maintaining over 80% cell viability. It inhibited integrase activity by 67%, specifically targeting the strand-transfer step, and significantly reduced integrated viral DNA. Molecular docking of 14 compounds identified coumarin derivatives as key bioactive metabolites, exhibiting mutation-tolerant binding within the integrase catalytic pocket. Overall, these findings highlight PO4PR2 as a promising source of compounds for developing new therapies targeting drug-resistant HIV-1 integrase. Full article

Background/Objectives: Achillea millefolium is a well-known medicinal plant recognized in several pharmacopeias, while the Balkan endemic species Achillea clypeolata lacks a pharmacopeial monograph and remains insufficiently studied despite its traditional use. This study aimed to comparatively evaluate the phytochemical composition and biological potential of both species. Methods: Chemical composition was studied using UHPLC-MS/MS, HPLC, and FT-IR; anti-inflammatory potential was analyzed by erythrocyte membrane stabilization assay (heat- and hypotonicity-induced hemolysis); and enzyme-inhibitory activity was tested against collagenase, elastase, hyaluronidase, and tyrosinase. In addition, antioxidant activity was evaluated using DPPH, ABTS, and DCFDA assays; antimicrobial activity was determined using the broth microdilution method; and cytotoxic potential was investigated by the MTT assay. Results: The major constituents in water–ethanolic extracts were quinic acid derivatives, flavonoids, phenolic acids, and coumarins, with chlorogenic acid, 3,5-dicaffeoylquinic acid, cosmosiin, cynaroside, rutin, and hyperoside as dominant in both species. Extracts exhibited marked anti-inflammatory activity, where A. millefolium provided greater protection under heat-induced hemolysis, and both extracts showed comparable efficacy under osmotic stress. Concentration-dependent inhibition of collagenase, elastase, hyaluronidase, and tyrosinase (concentration from 62.5 to 1000 µg/mL), along with significant antioxidant activity in ABTS and DPPH assays, was observed. In MRC-5 cells, the extracts reduced AAPH-induced ROS levels up to 50 µg/mL, while higher concentrations showed diminished effects. Moderate cytotoxicity was observed, with A. clypeolata displaying stronger effects at 50–100 µg/mL. Both Achillea species exhibited broad-spectrum antimicrobial activity, with pronounced effects against Gram-positive bacteria. Conclusions: The results support the traditional use of Achillea species and highlight A. clypeolata as a promising, yet underexplored, source of bioactive compounds for dermatological and pharmaceutical applications. Full article

Plants long employed in traditional medicine remain promising yet underexplored sources of antioxidant compounds. Montanoa bipinnatifida C. Koch, native to southern Mexico, is one such species with a largely uncharacterized chemical profile. In this study, a hydroethanolic of Montanoa bipinnatifida C. Koch leaf extract (MB-LE) was prepared via maceration with 70% ethanol, yielding 18% (w/w), and subsequently analyzed using spectroscopic and metabolomic approaches. UV–Vis and FTIR spectra revealed a chemically diverse matrix enriched in phenolic and nitrogen-containing constituents. High-resolution ESI-FT-ICR-MS profiling enabled the tentative identification of structurally varied metabolites, including alkaloids, saponins, glycosides, coumarins, and small peptides, while GC–MS analysis further indicated the presence of terpenoids and lipid-related compounds. These findings highlight a previously unrecognized chemical complexity in these species. Functionally, MB-LE exhibited moderate antioxidant activity in the DPPH, ABTS, and FRAP assays (IC₅₀ = 56.21 ± 0.67 µg/mL, 724.82 ± 27.49 µmol TE/g extract, and 614.90 ± 42.63 µmol TE/g extract, respectively), while the extract’s high phenolic content (333.31 ± 11.93 mg GAE/g extract) suggests a central role of these compounds in its observed activity. Overall, this work positions M. bipinnatifida as a novel source of bioactive metabolites and establishes a foundation for future studies focused on its structural elucidation and biological validation. Full article

Pseudopodospermum szowitzii (DC.) Kuth. a member of the Asteraceae family, grows naturally in the Irano-Turanian phytogeographical area, including Anatolia. In Anatolia, P. szowitsii, known as “goftigoda,” has edible young leaves and roots and is used in folk medicine for antidiabetic and analgesic properties. Nine compounds, including chlorogenic acid and derivatives from the ethyl acetate layer as well as 2,4,6-trimethoxyphenyl-1-O-β-glucopyranoside, 2,4,6-trimethoxyphenyl-1-O-β-apiofuranosyl-(1→6)-β-glucopyranoside, esculetin 6-O-β-glucopyranoside, and esculetin 6-O-β-apiofuranosyl-(1→6)-β-glucopyranoside from the water part of the methanolic extract, were isolated as known compounds. Notably, all esculetin derivatives have been isolated from the Pseudopodospermum for the first time, and among them, three compounds, esculetin 6-O-β-xylosyl-(1→6)-β-glucopyranoside, esculetin 6-O-β-glucopyranosyl-(1→3)-β-glucopyranoside, and esculetin 6-O-β-glucopyranosyl-(1→6)-β-glucopyranoside, were isolated as new esculetin heterosides that have not yet been isolated from any natural sources. The antioxidant activities of the total extract, phases, fractions, and compounds of P. szowitsii were also tested by evaluating their radical-scavenging capacities against DPPH and ABTS radicals. The ethyl acetate phase and the isolated compounds displayed significant antioxidant activity. The most active compound was caffeic acid, with IC₅₀ values of 2.7 µg/mL and 3.4 µg/mL against DPPH and ABTS radicals, respectively, followed by dicaffeoylquinic acid derivatives and their methyl esters. On the other hand, none of the coumarin derivatives exhibited significant radical-scavenging activity. Full article

Background: Carbonic Anhydrases (CAs) represent regulators of cell adaptation to hypoxia, pH regulation, and metabolic fitness. Among cancers, multiple myeloma (MM) is a plasma cell malignancy sustained by hypoxia-driven metabolic adaptation, extracellular acidification, and redox imbalance. Tight regulation of tumor extracellular pH, mediated by Carbonic Anhydrases IX and XII, is crucial for myeloma survival, progression, and stemness, making these isoforms attractive therapeutic targets. Methods: We designed and synthesized a library of terpenoid-based hybrids by derivatizing chlorothymol and 4-isopropyl-3-methylphenol with either the natural coumarin umbelliferon or the 2,2′-dipicolylamine (DPA) scaffold. This chemical strategy aimed to selectively inhibit tumor-associated CAs IX/XII through coumarin- or DPA-mediated recognition, while terpenoid fragments were introduced to enhance lipophilicity, membrane permeability, and potential redox-modulating properties. The compounds were tested by a Stopped-Flow assay for CA inhibition, in cell-based assays for antiproliferative properties and by means of several antioxidant assays. Results: The most active compounds, connecting the coumarin core to a terpenoid tail, inhibited the targeted CAs in the nanomolar range, showing up higher selectivity over off-target isoforms (I and II). In studies performed on MM cell lines, selected derivatives reduced viability (IC₅₀ = 15.8–85.4 µM) and displayed favorable selectivity over normal cells. In silico investigations suggested that the compounds were able to interact selectively with the target enzymes. Conclusions: Collectively, these results support a dual-targeting strategy in which selective inhibition of tumor-associated CAs, combined with redox modulation, interferes with adaptive mechanisms of MM cells, providing a rational framework for the development of multifunctional agents against metabolically resilient hematological malignancies. Full article

The synthesis of heterocyclic compounds such as pyridines, quinazolinones and coumarins is a fundamental area of organic chemistry due to their wide application in the pharmaceutical and chemical industries, agro-industry, and other fields of modern technology. As these compounds are produced in large quantities and have significant industrial importance, the development of sustainable and environmentally friendly synthetic approaches has become a key objective of green chemistry. In this context, this review examines the principles, methods and applications of the sustainable synthesis of pyridines, quinazolinones and coumarins in deep eutectic solvents (DESs), a new class of solvents characterized by low volatility, non-toxicity, ease of preparation and recyclability, often from renewable sources. Special emphasis is placed on synthetic strategies that achieve reaction efficiency while reducing environmental impact, including processes without additional catalysts or with reusable catalysts. The paper provides a comprehensive overview of recent advances and highlights the potential of DESs as a viable alternative to conventional organic solvents in the synthesis of bioactive pyridine, quinazolinone and coumarin compounds. Full article

Background/Objectives: The purpose of this study was the chemical design, synthesis, and evaluation of the antimicrobial and antibiofilm potentials of 20 novel thiazolyl-methylthio-thiadiazole hybrid compounds (6a–j and 8a–j). Methods: The compounds were designed as structural analogues of halicin with two points of variation and were synthesized through a process with multiple condensation steps. The compounds were evaluated in vitro through MIC determinations for the antimicrobial activity and percentage of biofilm inhibition, and in silico, respectively, through molecular docking, druggability, and ADMETox prediction. A 2D-QSAR study was conducted for antimicrobial activity using the Free-Wilson model. Results: In terms of antibacterial activity, all compounds displayed important activity on the tested strains (MICs = 15.62–250 μg/mL), except against Staphylococcus aureus. Regarding the antifungal activity, the effect against Candida albicans was similar to fluconazole in most cases (MIC = 15.62 μg/mL). With respect to the antibiofilm activity, the most effective activity was registered against the Pseudomonas aeruginosa biofilm. The in vitro results for the antibacterial activity against Escherichia coli were correlated with the observations drawn in the molecular docking study on the ATPase domain of the GyrB subunit of E. coli. The in silico predictions of the molecular properties concluded that all compounds have good druggability properties, while the ADMETox predictions concluded that the compounds could have low gastrointestinal absorption and blood–brain barrier permeation capacity, but raised safety flags (e.g., hepatotoxicity and high acute oral toxicity). The 2D-QSAR study concluded that the thiazolyl-methylthio-thiadiazole scaffold had the highest contribution to antimicrobial activity in almost all cases. Conclusions: The two series of compounds highlight the impact of structural modulations of the scaffold and its substituents on the investigated biological activities. Full article