Search Results (21)

Background/Objectives: In Brazil, Leishmania braziliensis is the main etiological agent of cutaneous leishmaniasis and represents an important public health problem. The actual pharmacotherapy of leishmaniasis has several disadvantages, making the development of new therapeutic options essential. The present study aimed to carry out the bioprospecting and selection of products of Amburana cearensis, including extracts and active principles with a leishmanicidal effect and to evaluate its possible mechanism of action. Methods: A dry extract of A. cearensis (DEAC) was characterized by HPLC, with the following active markers: coumarin (CM), amburoside A (AMR), and vanillic acid (VA). The leishmanicidal effect of DEAC was assessed, and the in vitro inhibitory action of the phenolic fraction, including CM, AMR, and VA, on promastigote and amastigote forms were determined. Results: CM showed the best reductions (maximal inhibition: 57%) of the promastigote form of L. braziliensis, followed by the plant extract (40% inhibition) and other test drugs (maximal reduction: 29%). The treatment of macrophages infected by L. brasiliensis with CM (10 μg/mL) reduced the intracellular parasite load (amastigote form, maximal reduction: 50%), increased the production of nitric oxide, TNF-α, IL-12, and IL-10, and decreased the production of IL-4. These effects were not related to cytotoxicity (MTT test). Glucantime (4 mg/mL, standard drug) reduced the amastigote form by 65%. Conclusions: CM showed promising leishmanicidal activity against both forms of L. brasiliensis, and this effect seems to be associated, at least in part, to its immunomodulatory action by tilting the Th1/Th2 imbalance in favor of Th1. Full article

Bacterial DNA gyrase is considered one of the validated targets for antibacterial drug discovery. Benzopyrones have been reported as promising derivatives that inhibit bacterial DNA gyrase B through competitive binding into the ATP binding site of the B subunit. In this study, we designed and synthesized twenty-two benzopyrone-based derivatives with different chemical features to assess their antimicrobial and photosensitizing activities. The antimicrobial activity was evaluated against B. subtilis, S. aureus, E. coli, and C. albicans. Compounds 6a and 6b (rigid tetracyclic-based derivatives), 7a-7f (flexible-linker containing benzopyrones), and 8a-8f (rigid tricyclic-based compounds) exhibited promising results against B. subtilis, S. aureus, and E. coli strains. Additionally, these compounds demonstrated photosensitizing activities against the B. subtilis strain. Both in silico molecular docking and in vitro DNA gyrase supercoiling inhibitory assays were performed to study their potential mechanisms of action. Compounds 8a-8f exhibited the most favorable binding interactions, engaging with key regions within the ATP binding site of the DNA gyrase B domain. Moreover, compound 8d displayed the most potent IC₅₀ value (0.76 μM) compared to reference compounds (novobiocin = 0.41 μM and ciprofloxacin = 2.72 μM). These results establish a foundation for structure-based optimization targeting DNA gyrase inhibition with antibacterial activity. Full article

Coumarins are benzopyrones found in several plant genera, including Pterocaulon (Asteraceae). These compounds represent an important source of new treatments, especially as antimicrobial and antifungal agents. In this study, two coumarin-rich extracts from Pterocaulon balansae using green technologies were obtained through aqueous maceration (AE) and supercritical fluid extraction (SFE). Such extracts were incorporated into nanoemulsions (NAE and NSFE) composed of a medium-chain triglyceride oil core stabilized by phospholipids. The nanoemulsions exhibited droplet sizes between 127 and 162 nm, pH above 5.0, and viscosity of approximately 1.0 cP, properties compatible with the topical route. The coumarins permeation/retention from formulations through ear porcine skin using Franz-type diffusion cells were evaluated. Whatever the extract, coumarins were distributed in skin layers, especially in the dermis in both intact and impaired (tape stripping) skin. In addition, a significant increase in coumarins that reached up to the receptor fluid was observed for impaired skin, with increases of approximately threefold for NAE and fourfold for NSFE. Finally, antifungal activity of nanoemulsions was evaluated according to minimum inhibitory concentrations, and the values were 250 µg/mL for all strains tested. The overall results demonstrated the feasibility of incorporating P. balansae extracts into nanoemulsions and showed a potential alternative for the treatment of sporotrichosis. Full article

This work deals with the study of the release and antioxidant activity kinetics of three natural antioxidants associated as binary mixture (coumarin, and/or gallic acid and rutin) from chitosan films. Antioxidants were incorporated into film alone or in binary mixture. The aim was to determine the influence of rutin on the phenolic acid and benzopyrone. The UV-visible light transmission spectra of the films were also investigated. Neat chitosan films and chitosan incorporated coumarin exhibited high transmittance in the UV-visible light range, while GA-added chitosan films showed excellent UV light barrier properties. The molecular interactions between chitosan network and antioxidants were confirmed by FTIR where spectra displayed a shift of the amide-III peak. Rutin has a complex structure that can undergo ionization. The chitosan network structure induced change was found to influence the release behavior. The film containing rutin showed the highest antioxidant activity (65.58 ± 0.26%), followed by gallic acid (44.82 ± 3.73%), while coumarin displayed the lowest activity (27.27 ± 4.04%). The kinetic rate against DPPH-free radical of rutin is three times higher than coumarin. The kinetic rates were influenced by the structure and interactions of the antioxidants with chitosan. Rutin exhibited a slow release due to its molecular interactions with chitosan, while coumarin and gallic acid showed faster release. The diffusion coefficient of coumarin is 900 times higher than that of rutin. The rutin presence significantly delayed the release of the gallic acid and coumarin, suggesting an antagonistic effect. However, their presence weakly affects the release behavior of rutin. Full article

The genus Dipteryx, to which the cumaru tree belongs, contains neotropical species native to Central and South American countries. They are used both in the sale of timber and seeds and for the extraction of the active compound coumarin, used as a flavoring agent. This study evaluated the phytochemical profile and antioxidant activity of extracts of leaves, branches, and fruits (residues and seeds) of the species Dipteryx punctata. The plant material for analysis was collected in five seed-producing areas, in Mojuí dos Campos, Pará, Brazil. The extracts were obtained via Soxhlet extractor using 92.8% distilled ethanol as the solvent and operated till exhaustion (8 h). Chromatographic analyses were performed by thin-layer chromatography (TLC) and gas chromatography coupled to mass spectrometry (GC-MS), followed by phytochemical determination of phenolics and flavonoids and analysis of antioxidant activity (TLC and free radical scavenging 2,2-diphenyl-1-picrylhydrazyl (DPPH). The highest extract yields were obtained from D. punctata fruit residues and seeds from all areas, with maximum values of 26.1% and 47.2%, respectively, in Boa Fé (area 3). In the evaluation by TLC, the extracts of leaves, branches, and residues presented the classes of terpenes, condensed and hydrolysable tannins, and flavonoids; coumarin (1,2-benzopyrone) was identified only in residue and seed extracts. The major constituents highlighted in the collection areas were: lupeol in leaves (34.4% in area 5), 4-O-methylmannose in branches and residues (85.5% in area 2 and 90.6% in area 5, respectively), and coumarin in seeds (99.3% in area 3). The best results for the antioxidant action were obtained for extracts from leaves and residues, requiring a concentration of 117.6 µg.mL⁻¹ of the extract from the leaves and 160.4 µg.mL⁻¹ of the extract from the residues to reduce the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical by 50%. This phytochemical study contributes to reducing the scarcity of information on D. punctata. The chemical classes and compounds identified corroborate the antioxidant activity and add value to the species, and the data obtained reinforce the importance of reusing fruit residues, which are chemically rich but discarded in the environment. Full article

Weed and soil-borne pathogens could synergistically affect vegetable growth and result in serious losses. Investigation of agricultural bioactive metabolites from marine-derived fungus Alternaria iridiaustralis yielded polyketides (1–4), benzopyrones (5–7), meroterpenoid derivatives (8), and alkaloid (9). The structures and absolute configurations of new 1, 3, 5–6, and 8 were elucidated by extensive spectroscopic analyses, as well as comparisons between measured and calculated ECD and ¹³C NMR data. Compounds 1–4, 6, and 9 showed herbicidal potentials against the radicle growth of Echinochloa crusgalli seedlings. Especially 9 exhibited inhibition rates over 90% at concentrations of 20 and 40 μg/mL, even better than the commonly used chemical herbicide acetochlor. Furthermore, 9 also performed a wide herbicidal spectrum against the malignant weeds Digitaria sanguinalis, Portulaca oleracea, and Descurainia sophia. Compounds 5–8 showed antifungal activities against carbendazim-resistant strains of Botrytis cinerea, with minimum inhibitory concentration (MIC) values ranging from 32 to 128 μg/mL, which were better than those of carbendazim (MIC = 256 μg/mL). Especially 6 exhibited integrated effects against both soil-borne pathogens and weed. Overall, marine-derived fungus A. iridiaustralis, which produces herbicidal and antifungal metabolites 1–9, showed the potential for use as a microbial pesticide to control both weed and soil-borne pathogens. Full article

In this work, a novel bio-based high-performance bisbenzoxazine resin was synthesized from daidzein, 2-thiophenemethylamine and paraformaldehyde. The chemical structure was confirmed using nuclear magnetic resonance spectroscopy (NMR) and Fourier-transform infrared spectroscopy (FT-IR). The polymerization process was systematically studied using differential scanning calorimetry (DSC) and in situ FT-IR spectra. It can be polymerized through multiple polymerization behaviors under the synergistic reaction of thiophene rings with benzopyrone rather than a single polymerization mechanism of traditional benzoxazines, as reported. In addition, thermogravimetric analysis (TGA) and a microscale combustion calorimeter (MCC) were used to study the thermal stability and flame retardancy of the resulting polybenzoxazine. The thermosetting material showed a high carbon residue rate of 62.8% and a low heat release capacity (HRC) value of 33 J/gK without adding any flame retardants. Based on its outstanding capability of carbon formation, this newly obtained benzoxazine resin was carbonized and activated to obtain a porous carbon material doped with both sulfur and nitrogen. The CO₂ absorption of the carbon material at 0 °C and 25 °C at 1 bar was 3.64 mmol/g and 3.26 mmol/g, respectively. The above excellent comprehensive properties prove its potential applications in many advanced fields. Full article

Coumarin is an effective treatment for primary lymphoedema, as well as lymphoedema related to breast cancer radiotherapy or surgery. However, its clinical use is limited in several countries due to the possible occurrence of hepatotoxicity, mainly in the form of mild to moderate transaminase elevation. It is worth noting that only a few cases of severe hepatotoxicity have been described in the literature, with no reported cases of liver failure. Data available on coumarin absorption, distribution, metabolism, and excretion have been reviewed, focusing on hepatotoxicity studies carried out in vitro and in vivo. Finally, safety and tolerability data from clinical trials have been thoroughly discussed. Based on these data, coumarin-induced hepatotoxicity is restricted to a small subset of patients, probably due to the activation in these individuals of alternative metabolic pathways involving specific CYP450s isoforms. The aim of this work is to stimulate research to clearly identify patients at risk of developing hepatotoxicity following coumarin treatment. Early identification of this subset of patients could open the possibility of more safely exploiting the therapeutical properties of coumarin, allowing patients suffering from lymphoedema to benefit from the anti-oedematous activity of the treatment. Full article

Esculetin is a coumarin compound, which belongs to the class of benzopyrone enriched in various plants such as Sonchus grandifolius, Aesculus turbinata, etc. Free radicals lead to the development of oxidative stress causing inflammation, arthritis, cancer, diabetes, fatty liver disease, etc. These further reduce the efficacy of anticancer drugs, activate inflammatory signaling pathways, degrade joints and cartilage, and disrupt the glycemic index and normal function of liver enzymes. For instance, the current treatment modalities used in arthritis such as non-steroidal anti-inflammatory drugs, disease-modifying anti-rheumatoid drugs, and lipoxygenase inhibitors present limited efficacy and adverse effects. Thus, there is a constant need to find newer and safer alternatives. Esculetin has an immense antioxidative potential thereby alleviating arthritis, diabetes, malignancies, and hepatic disorders. Structurally, esculetin contains two hydroxyl groups, which enhance its ability to function as an antioxidant by inhibiting oxidative stress in pathological conditions. Leukotriene B4 synthesis, NF-κB and MPAK pathway activation, and inflammatory cytokine production are the main causes of bone and joint deterioration in arthritis, whereas esculetin treatment reverses these factors and relieves the disease condition. In contrast, lipid peroxidation caused by upregulation of TGF-β-mediated expression and dysfunction of antioxidant enzymes is inhibited by esculetin therapy, thus reducing liver fibrosis by acting on the PI3K/FoxO1 pathway. Therefore, targeting NF-κB, pro-inflammatory cytokines, TGF-β and oxidative stress may be a therapeutic strategy to alleviate arthritis and liver fibrosis. Full article

Dipteryx odorata and Dipteryx punctata are species native to the Amazonian, traded by extractivists to obtain coumarin. We aimed to analyze the presence of coumarin in the ethanolic extracts of leaves, branches and fruits of D. odorata and D. punctata and to evaluate the antimicrobial activity of these extracts against phytopathogenic fungi and bacteria of clinical interest. Chemical analyses were performed by thin layer chromatography (TLC) and by gas chromatography coupled to mass spectrometry (GC-MS). For the antifungal assays, the fungi used were Cercospora longissima, Colletotrichum gloeosporioides, two isolates of Fusarium spp. and Sclerotium rolfsii, and the antibacterial assay was performed using the minimum inhibitory concentration (MIC) test with Burkholderia cepacia, Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus bacteria. In D. odorata seed extracts and in D. punctata husks, endocarps, and seeds, we identified 1,2-benzopyrone. D. odorata endocarp extracts and D. punctata seeds provided the greatest decrease in mycelial growth of the evaluated phytopathogens, showing promise as an alternative control. The husk and endocarp extracts of both species had a weak effect on E. coli. This research is the first to compare the different parts of species of the genus Dipteryx and to evaluate the use of husks and endocarps of D. punctata fruits to obtain coumarin. Chemical analyses used to quantify the compounds existing in the extracts, and tests with phytopathogens in vitro and in vivo are currently being carried out. Full article

Coumarins are a structurally varied set of 2H-chromen-2-one compounds categorized also as members of the benzopyrone group of secondary metabolites. Coumarin derivatives attract interest owing to their wide practical application and the unique reactivity of fused benzene and pyrone ring systems in molecular structure. Coumarins have their own specific fingerprints as antiviral, antimicrobial, antioxidant, anti-inflammatory, antiadipogenic, cytotoxic, apoptosis, antitumor, antitubercular, and cytotoxicity agents. Natural products have played an essential role in filling the pharmaceutical pipeline for thousands of years. Biological effects of natural coumarins have laid the basis of low-toxic and highly effective drugs. Presently, more than 1300 coumarins have been identified in plants, bacteria, and fungi. Fungi as cultivated microbes have provided many of the nature-inspired syntheses of chemically diverse drugs. Endophytic fungi bioactivities attract interest, with applications in fields as diverse as cancer and neuronal injury or degeneration, microbial and parasitic infections, and others. Fungal mycelia produce several classes of bioactive molecules, including a wide group of coumarins. Of promise are further studies of conditions and products of the natural and synthetic coumarins’ biotransformation by the fungal cultures, aimed at solving the urgent problem of searching for materials for biomedical engineering. The present review evaluates the fungal coumarins, their structure-related peculiarities, and their future therapeutic potential. Special emphasis has been placed on the coumarins successfully bioprospected from fungi, whereas an industry demand for the same coumarins earlier found in plants has faced hurdles. Considerable attention has also been paid to some aspects of the molecular mechanisms underlying the coumarins’ biological activity. The compounds are selected and grouped according to their cytotoxic, anticancer, antibacterial, antifungal, and miscellaneous effects. Full article

Coumarin is a naturally occurring lactone-type benzopyrone with various applications in the pharmaceutical, food, perfume, and cosmetics industries. This hydrophobic compound is poorly soluble in water but dissolves well in protic organic solvents such as alcohols. Despite the extensive use of coumarin, there are only a few reports documenting its solubility in organic solvents, and some reported data are incongruent, which was the direct impulse for this study. To resolve this problem, a theoretical congruency test was formulated using COSMO-RS-DARE for the determination of intermolecular interaction parameters, which allowed for the identification of outliers as suspicious datasets. The perfect match between back-computed values of coumarin solubility and the experimental ones confirms the reliability of the formulated theoretical approach and its adequacy for testing solubility data consistency. As the final approval, the temperature-related coumarin solubility in seven neat alcohols was determined experimentally. Four solvents (methanol, ethanol, 1-propanol, and 2-propanol) were used for reproducibility purposes, and an additional three (1-butanol, 1-pentanol, and 1-octanol) were used to extend the information on the homologous series. The consistency of this extended solubility dataset is discussed in terms of the comparison of remeasured solubility values with the ones already published and within the series of structurally similar solvents. The proposed procedure extends the range of applicability of COSMO-RS-DARE and provides a real and useful tool for consistency tests of already published solubility data, allowing for the approval/disapproval of existing data and filling gaps in datasets. Linear regressions utilizing a 2D molecular descriptor, SpMin2_Bhm, or the distance between solute and solvent in the Hansen solubility space, R_a, were formulated for the estimation of COMSO-RS-DARE integration parameters. Full article

Coumarin is highly distributed in nature, notably in higher plants. The biological features of coumarin include antibacterial, anticancer and antioxidant effects. It is well known that metal ions present in complexes accelerate the drug action and the efficacy of organic therapeutic agents. The main aim of the current study is the synthesis of different complexes of the interaction between ciprofloxacin hydrochloride (CIP) and coumarin derivative 7-hydroxy-4-methylcoumarin (HMC) with Zr(IV). The chelates of CIP with Zr(IV) were prepared and characterized by elemental analysis, melting point, conductance measurements, spectroscopic techniques involving IR, UV-Vis, ¹H NMR, and thermal behavior (TG-DTG) in the presence of HMC, dimethylformamide (DMF), pyridine (Py), and triethylamine (Et₃N). Results of molar conductivity tests showed that the new synthesized complexes are electrolytes with a 1:1 or 1:2 electrolyte ratio, with the chloride ions functioning as counter ions. According to IR spectra, CIP acts as a neutral bidentate ligand with Zr(IV) through one carboxylato oxygen and the carbonyl group, HMC as a monodentate through the carbonyl group, and DMF through the oxygen atom of the carbonyl group and the N atom of Py and Et₃N. The thermal behavior of the complexes was carefully investigated using TG and DTG techniques. TG findings signal that water molecules are found as hydrated and coordinated. The thermal decomposition mechanisms proposed for CIP, HMC, and Zr(IV) complexes are discussed and the activation energies (E_a), Gibbs free energies (∆G*), entropies (∆S*), and enthalpies (∆H*) of thermal decomposition reactions have been calculated using Coats–Redfern (CR) and Horowitz–Metzeger (HM) methods. The studied complexes were tested against some human pathogens and phytopathogens, including three Gram-positive bacteria (Bacillus subtilis, B. cereus, Brevibacterium otitidis) and three Gram-negative bacteria (Escherichiacoli, Pseudomonas aeruginosa and Klebsiella pneumoniae), and compared to the free CIP and HMC parent compounds. Full article

Coumarins are natural heterocycles that widely contribute to the design of various biologically active compounds. Fusing different aromatic heterocycles with coumarin at its 3,4-position is one of the interesting approaches to generating novel molecules with various biological activities. During our continuing interest in assembling information about fused five-membered aromatic heterocycles, and after having presented mono-hetero-atomic five-membered aromatic heterocycles in Part I. The current review Part II is intended to present an overview of the different synthetic routes to coumarin (benzopyrone)-fused five-membered aromatic heterocycles with multi-heteroatoms built on the pyrone ring, covering the literature from 1945 to 2021. Full article