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Molecules (Basel, Switzerland) Oct 2021Coumarins are widely distributed in nature and can be found in a large number of naturally occurring and synthetic bioactive molecules [...].
Coumarins are widely distributed in nature and can be found in a large number of naturally occurring and synthetic bioactive molecules [...].
Topics: Coumarins; Humans
PubMed: 34684900
DOI: 10.3390/molecules26206320 -
Biochimica Et Biophysica Acta. Proteins... Sep 2020Coumarins represent well-established structures to introduce fluorescence into tool compounds for biochemical investigations. They are valued for their small size,... (Review)
Review
Coumarins represent well-established structures to introduce fluorescence into tool compounds for biochemical investigations. They are valued for their small size, chemical stability and accessibility as well as their tunable photochemical properties. As components of fluorophore/quencher pairs or FRET donor/acceptor pairs, coumarins have frequently been applied in substrate mapping approaches for serine and cysteine proteases. This review also focuses on the incorporation of coumarins into the side chain of amino acids and the exploitation of the resulting fluorescent amino acids for the positional profiling of protease substrates. The protease-inhibiting properties of certain coumarin derivatives and the utilization of coumarin moieties to assemble activity-based probes for serine and cysteine proteases are discussed as well.
Topics: Catalytic Domain; Coumarins; Cysteine Proteases; Fluorescence; Fluorescence Resonance Energy Transfer; Fluorescent Dyes; Serine; Serine Proteases; Substrate Specificity
PubMed: 32405284
DOI: 10.1016/j.bbapap.2020.140445 -
Molecules (Basel, Switzerland) Jan 2021Inflammatory bowel disease (IBD) is a non-communicable disease characterized by a chronic inflammatory process of the gut and categorized into Crohn's disease and... (Review)
Review
Inflammatory bowel disease (IBD) is a non-communicable disease characterized by a chronic inflammatory process of the gut and categorized into Crohn's disease and ulcerative colitis, both currently without definitive pharmacological treatment and cure. The unclear etiology of IBD is a limiting factor for the development of new drugs and explains the high frequency of refractory patients to current drugs, which are also related to various adverse effects, mainly after long-term use. Dissatisfaction with current therapies has promoted an increased interest in new pharmacological approaches using natural products. Coumarins comprise a large class of natural phenolic compounds found in fungi, bacteria, and plants. Coumarin and its derivatives have been reported as antioxidant and anti-inflammatory compounds, potentially useful as complementary therapy of the IBD. These compounds produce protective effects in intestinal inflammation through different mechanisms and signaling pathways, mainly modulating immune and inflammatory responses, and protecting against oxidative stress, a central factor for IBD development. In this review, we described the main coumarin derivatives reported as intestinal anti-inflammatory products and its available pharmacodynamic data that support the protective effects of these products in the acute and subchronic phase of intestinal inflammation.
Topics: Animals; Biological Products; Coumarins; Humans; Inflammatory Bowel Diseases; Protective Agents
PubMed: 33467396
DOI: 10.3390/molecules26020422 -
Molecules (Basel, Switzerland) Dec 2022Coumarin is an effective treatment for primary lymphoedema, as well as lymphoedema related to breast cancer radiotherapy or surgery. However, its clinical use is limited... (Review)
Review
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.
Topics: Humans; Chemical and Drug Induced Liver Injury; Coumarins; Risk Assessment; Lymphedema
PubMed: 36558195
DOI: 10.3390/molecules27249063 -
Molecules (Basel, Switzerland) Jun 2017This review covers the synthesis of coumarin-porphyrin, coumarin-phthalocyanine and coumarin-corrole conjugates and their potential applications. While... (Review)
Review
This review covers the synthesis of coumarin-porphyrin, coumarin-phthalocyanine and coumarin-corrole conjugates and their potential applications. While coumarin-phthalocyanine conjugates were obtained almost exclusively by tetramerization of coumarin-functionalized phthalonitriles, coumarin-porphyrin and coumarin-corrole conjugates were prepared by complementary approaches: (a) direct synthesis of the tetrapyrrolic macrocycle using formylcoumarins and pyrrole or (b) by functionalization of the tetrapyrrolic macrocycle. In the last approach a range of reaction types were used, namely 1,3-dipolar cycloadditions, hetero-Diels-Alder, Sonogashira, alkylation or acylation reactions. This is clearly a more versatile approach, leading to a larger diversity of conjugates and allowing the access to conjugates bearing one to up to 16 coumarin units.
Topics: Alkylation; Coumarins; Indoles; Isoindoles; Molecular Structure; Porphyrins; Pyrroles
PubMed: 28617340
DOI: 10.3390/molecules22060994 -
Molecules (Basel, Switzerland) Aug 2022Coumarins are fused six-membered oxygen-containing benzoheterocycles that join two synthetically useful rings: α-pyrone and benzene. A survey of the literature shows... (Review)
Review
Coumarins are fused six-membered oxygen-containing benzoheterocycles that join two synthetically useful rings: α-pyrone and benzene. A survey of the literature shows that coumarins and their metal complexes have received great interest from synthetic chemists, medicinal scientists, and pharmacists due to their wide spectrum of biological applications. For instance, coumarin and its derivatives have been used as precursors to prepare a large variety of medicinal agents. Likewise, coumarin-derived imine-metal complexes have been found to display a variety of therapeutic applications, such as antibacterial, antifungal, anticancer, antioxidant, anthelmintic, pesticidal, and nematocidal activities. This review highlights the current synthetic methodologies and known bioactivities of coumarin-derived imine-metal complexes that make this molecule a more attractive scaffold for the discovery of newer drugs.
Topics: Antioxidants; Coordination Complexes; Coumarins; Imines
PubMed: 36014460
DOI: 10.3390/molecules27165220 -
Molecules (Basel, Switzerland) Feb 2020In order to facilitate the development of the green subcritical water chromatography technique for vanillin and coumarin, the stability of the compounds under...
In order to facilitate the development of the green subcritical water chromatography technique for vanillin and coumarin, the stability of the compounds under subcritical water conditions was investigated in this work. In addition, their extraction from natural products was also studied. The stability experiments were carried out by heating the mixtures of vanillin and water or coumarin and water at temperatures ranging from 100 °C to 250 C, while subcritical water extractions (SBWE) of both analytes from vanilla beans and whole tonka beans were conducted at 100 C to 200 C. Analyte quantification for both stability and extraction studies was carried out by HPLC. After heating for 60 min, vanillin was found to be stable in water at temperatures up to 250 C. While coumarin is also stable at lower temperatures such as 100 °C and 150 C, it undergoes partial degradation after heating for 60 min at 200 C and higher. The results of this stability study support green subcritical water chromatographic separation and extraction of vanillin and coumarin at temperatures up to 150 C. The SBWE results revealed that the extraction efficiency of both analytes from vanilla beans and tonka beans is significantly improved with increasing temperature.
Topics: Benzaldehydes; Chromatography, High Pressure Liquid; Coumarins; Hot Temperature; Plant Extracts; Sonication; Water
PubMed: 32120972
DOI: 10.3390/molecules25051061 -
Molecules (Basel, Switzerland) Jan 2021Coumarins are naturally occurring molecules with a versatile range of activities. Their structural and physicochemical characteristics make them a privileged scaffold in... (Review)
Review
Coumarins are naturally occurring molecules with a versatile range of activities. Their structural and physicochemical characteristics make them a privileged scaffold in medicinal chemistry and chemical biology. Many research articles and reviews compile information on this important family of compounds. In this overview, the most recent research papers and reviews from 2020 are organized and analyzed, and a discussion on these data is included. Multiple electronic databases were scanned, including SciFinder, Mendeley, and PubMed, the latter being the main source of information. Particular attention was paid to the potential of coumarins as an important scaffold in drug design, as well as fluorescent probes for decaging of prodrugs, metal detection, and diagnostic purposes. Herein we do an analysis of the trending topics related to coumarin and its derivatives in the broad field of drug discovery.
Topics: Coumarins; Humans; Drug Discovery; Fluorescent Dyes; Drug Design
PubMed: 33477785
DOI: 10.3390/molecules26020501 -
The New Phytologist Feb 2021Iron (Fe) is a major micronutrient and is required for plant growth and development. Nongrass species have evolved a reduction-based strategy to solubilize and take up...
Iron (Fe) is a major micronutrient and is required for plant growth and development. Nongrass species have evolved a reduction-based strategy to solubilize and take up Fe. The secretion of Fe-mobilizing coumarins (e.g. fraxetin, esculetin and sideretin) by plant roots plays an important role in this process. Although the biochemical mechanisms leading to their biosynthesis have been well described, very little is known about their cellular and subcellular localization or their mobility within plant tissues. Spectral imaging was used to monitor, in Arabidopsis thaliana, the in planta localization of Fe-mobilizing coumarins and scopolin. Molecular, genetic and biochemical approaches were also used to investigate the dynamics of coumarin accumulation in roots. These approaches showed that root hairs play a major role in scopoletin secretion, whereas fraxetin and esculetin secretion occurs through all epidermis cells. The findings of this study also showed that the transport of coumarins from the cortex to the rhizosphere relies on the PDR9 transporter under Fe-deficient conditions. Additional experiments support the idea that coumarins move throughout the plant body via the xylem sap and that several plant species can take up coumarins present in the surrounding media. Altogether, the data presented here demonstrate that coumarin storage and accumulation in roots is a highly complex and dynamic process.
Topics: Arabidopsis; Arabidopsis Proteins; Coumarins; Plant Roots
PubMed: 33205512
DOI: 10.1111/nph.17090 -
Medicine Oct 2023Esculin and esculetin are 2 widely studied coumarin components of Cortex Fraxini, which is a well-known herbal medicine with a 2000-year history. In vivo and in vitro... (Review)
Review
Esculin and esculetin are 2 widely studied coumarin components of Cortex Fraxini, which is a well-known herbal medicine with a 2000-year history. In vivo and in vitro studies have demonstrated that both have a variety of pharmacological activities, including antioxidant, anti-tumor, anti-inflammatory, antibacterial, antidiabetic, immunomodulatory, anti-atherosclerotic, and so on. Their underlying mechanisms of action and biological activities include scavenging free radicals, modulating the nuclear factor erythroid 2-related factor 2 pathway, regulating the cell cycle, inhibiting tumor cell proliferation and migration, promoting mitochondrial pathway apoptosis, inhibiting the NF-κB and MAPK signaling pathways, regulating CD4+ T cells differentiation and associated cytokine release, inhibiting vascular smooth muscle cells, etc. This review aims to provide comprehensive information on pharmacological studies of esculin and esculetin, which is of noteworthy importance in exploring the therapeutic potential of both coumarin compounds.
Topics: Humans; Esculin; Umbelliferones; Coumarins; Apoptosis
PubMed: 37800835
DOI: 10.1097/MD.0000000000035306