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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 -
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: Chemistry, Pharmaceutical; Coumarins; Drug Discovery; Humans
PubMed: 33477785
DOI: 10.3390/molecules26020501 -
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) Feb 2022Coumarin is an important six-membered aromatic heterocyclic pharmacophore, widely distributed in natural products and synthetic molecules. The versatile and unique... (Review)
Review
Coumarin is an important six-membered aromatic heterocyclic pharmacophore, widely distributed in natural products and synthetic molecules. The versatile and unique features of coumarin nucleus, in combination with privileged sulfonamide moiety, have enhanced the broad spectrum of biological activities. The research and development of coumarin, sulfonamide-based pharmacology, and medicinal chemistry have become active topics, and attracted the attention of medicinal chemists, pharmacists, and synthetic chemists. Coumarin sulfonamide compounds and analogs as clinical drugs have been used to cure various diseases with high therapeutic potency, which have shown their enormous development value. The diversified and wide array of biological activities such as anticancer, antibacterial, anti-fungal, antioxidant and anti-viral, etc. were displayed by diversified coumarin sulfonamides. The present systematic and comprehensive review in the current developments of synthesis and the medicinal chemistry of coumarin sulfonamide-based scaffolds give a whole range of therapeutics, especially in the field of oncology and carbonic anhydrase inhibitors. In the present review, various synthetic approaches, strategies, and methodologies involving effect of catalysts, the change of substrates, and the employment of various synthetic reaction conditions to obtain high yields is cited.
Topics: Antineoplastic Agents; Carbonic Anhydrase Inhibitors; Coumarins; Structure-Activity Relationship; Sulfonamides
PubMed: 35268704
DOI: 10.3390/molecules27051604 -
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 -
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 -
Journal of Natural Products May 2021A set of 12 maslinic acid-coumarin conjugates was synthesized, with 9 being maslinic acid-diamine-coumarin conjugates at the C-28 carboxylic acid group of triterpene...
A set of 12 maslinic acid-coumarin conjugates was synthesized, with 9 being maslinic acid-diamine-coumarin conjugates at the C-28 carboxylic acid group of triterpene acid and the other three being maslinic acid-coumarin conjugates at C-2/C-3 and/or C-28 of the triterpene skeleton. The cytotoxic effects of these 12 triterpene conjugates were evaluated in three cancer cell lines (B16-F10, HT29, and Hep G2) and compared, respectively, with three nontumor cell lines from the same or similar tissue (HPF, IEC-18, and WRL68). The most potent cytotoxic results were achieved by a conjugate with two molecules of coumarin-3-carboxylic acid coupled through the C-2 and C-3 hydroxy groups of maslinic acid. This conjugate showed submicromolar IC values in two of the three cancer cell lines tested (0.6, 1.1, and 0.9 μM), being between 110- and 30-fold more effective than its corresponding precursor. Furthermore, this conjugate () showed percentages of cell viability for the three nontumor lines of 90%. Four maslinic acid-coumarin conjugates displayed apoptotic effects in the treated cells, with total apoptosis rates of between 40 and 85%, relative to the control. Almost all the compounds assayed caused cell-cycle arrest in all cancer cell lines, increasing the number of these cells in the G0/G1 phase.
Topics: Animals; Antineoplastic Agents; Cell Cycle Checkpoints; Coumarins; HT29 Cells; Hep G2 Cells; Humans; Melanoma, Experimental; Membrane Potential, Mitochondrial; Mice; Molecular Structure; Olive Oil; Triterpenes
PubMed: 33956447
DOI: 10.1021/acs.jnatprod.1c00128 -
Biomolecules Jun 2021A series of thiosemicarbazone-coumarin hybrids ( and ) has been synthesised in 12 steps and used for the preparation of mono- and dinuclear copper(II) complexes, namely...
A series of thiosemicarbazone-coumarin hybrids ( and ) has been synthesised in 12 steps and used for the preparation of mono- and dinuclear copper(II) complexes, namely (), (), () and (), isolated in hydrated or solvated forms. Both the organic hybrids and their copper(II) and dicopper(II) complexes were comprehensively characterised by analytical and spectroscopic techniques, i.e., elemental analysis, ESI mass spectrometry, 1D and 2D NMR, IR and UV-vis spectroscopies, cyclic voltammetry (CV) and spectroelectrochemistry (SEC). Re-crystallisation of from methanol afforded single crystals of copper(II) complex with monoanionic ligand , which could be studied by single crystal X-ray diffraction (SC-XRD). The prepared copper(II) complexes and their metal-free ligands revealed antiproliferative activity against highly resistant cancer cell lines, including triple negative breast cancer cells MDA-MB-231, sensitive COLO-205 and multidrug resistant COLO-320 colorectal adenocarcinoma cell lines, as well as in healthy human lung fibroblasts MRC-5 and compared to those for triapine and doxorubicin. In addition, their ability to reduce the tyrosyl radical in mouse R2 protein of ribonucleotide reductase has been ascertained by EPR spectroscopy and the results were compared with those for triapine.
Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Coordination Complexes; Copper; Coumarins; Crystallography, X-Ray; Humans; Mice; Models, Molecular; Molecular Structure; Pyridines; Structure-Activity Relationship; Thiosemicarbazones
PubMed: 34207929
DOI: 10.3390/biom11060862