Privileged structures have been widely used as an effective template for the research and discovery of high value chemicals. Coumarin is a simple scaffold widespread in Nature and it can be found in a considerable number of plants as well as in some fungi and bacteria. In the last years, these natural compounds have been gaining an increasing attention from the scientific community for their wide range of biological activities, mainly due to their ability to interact with diverse enzymes and receptors in living organisms. In addition, coumarin nucleus has proved to be easily synthetized and decorated, giving the possibility of designing new coumarin-based compounds and investigating their potential in the treatment of various diseases. The versatility of coumarin scaffold finds applications not only in medicinal chemistry but also in the agrochemical field as well as in the cosmetic and fragrances industry. This review is intended to be a critical overview on coumarins, comprehensive of natural sources, metabolites, biological evaluations and synthetic approaches.

An overview of coumarin as a versatile and readily accessible scaffold with broad-ranging biological activities

Many natural coumarins and their chemically synthesized analogs and derivatives exert diverse properties, such as anticancer, antioxidant, anti-inflammatory, or anticoagulant, with the latter being of the utmost importance. The widely used warfarin, acenocoumarol, and phenprocoumon exert anticoagulant properties by inhibiting the vitamin K epoxide reductase complex. In this interdisciplinary review, we present biochemical principles of the coagulation processes and possible methods for their tuning based on the use of coumarins. We also summarize chemical methods of synthesis of coumarins and discuss structures and properties of those that have been used for a long time, as well as newly synthesized compounds. Brief information on the clinical use of coumarins and other anticoagulant drugs is given, including the severe effects of overdosing and methods for reversing their action.

https://www.mdpi.com/1420-3049/25/6/1465/pdf

Antagonists of Vitamin K—Popular Coumarin Drugs and New Synthetic and Natural Coumarin Derivatives

Many populations suffer from thrombotic disorders such as stroke, myocardial infarction, unstable angina and thromboembolic disease. Thrombus is one of the major threatening factors to human health and the prevalence of cardio-cerebrovascular diseases induced by thrombus is growing worldwide, even some persons got rare and severe blood clots after receiving the AstraZeneca COVID vaccine unexpectedly. In terms of mechanism of thrombosis, antithrombotic drugs have been divided into three categories including anticoagulants, platelet inhibitors and fibrinolytics. Nowadays, a large number of new compounds possessing antithrombotic activities are emerging in an effort to remove the inevitable drawbacks of previously approved drugs such as the high risk of bleeding, a slow onset of action and a narrow therapeutic window. In this review, we describe the causes and mechanisms of thrombus formation firstly, and then summarize these reported active compounds as potential antithrombotic candidates based on their respective mechanism, hoping to promote the development of more effective bioactive molecules for treating thrombotic disorders. 

/pdf/progress-of-thrombus-formation-and-research-on-the-structure-1eu4ukx6.pdf

Progress of thrombus formation and research on the structure-activity relationship for antithrombotic drugs

Peroxodisulfate-assisted three-component benzylation of coumarins with styrenes and KSCN: a transition-metal-free approach for the synthesis of 3-(1-aryl-2-thiocyanatoethyl)-2H-chromen-2-one in ethyl lactate

The aim of this study was to investigate the effects of extracts and pure Artemisia dracunculus L (tarragon) metabolites on the antimonoamine oxidase and anticholinesterase activities The compounds were characterized as stigmasterol (1), herniarin (2), (2E,4E)-1-(piperidin-1-yl)undeca-2,4-diene-8,10-diyn-1-one (3), (2E,4E)-N-isobutylundeca-2,4-dien-8,10-diynamide (4), 3,4-dehydroherniarin (5) and skimmin (6) by 1H-NMR, 13C-NMR, 1D and 2D NMR methods The compounds 5 and 6 were isolated from tarragon for the first time The extracts and pure compounds have inhibitory effects on the human monoamine oxidase (hMAO) A and B enzymes, whereas they did not exhibit any anticholinesterase activities Among the tarragon compounds, only 2 and 6 compounds showed the inhibitory effects against hMAO A (IC50 = 5176 and 7347 μM, respectively) and hMAO B (IC50 = 084 and 163 mM, respectively) In the study, herniarin content in the extracts was also analysed by high-performance liquid chromatography and it was found that there was a relationship between the inhibition effects of the extracts and their herniarin content

human monoamine oxidase (hMAO) A and hMAO B inhibitors from Artemisia dracunculus L. herniarin and skimmin: human mononamine oxidase A and B inhibitors from A. dracunculus L.

A synthetic method for a series of new coumarin conjugates was developed. Their structures and physicochemical properties were determined by modern spectral methods (IR, NMR, ESI-MS). The anticoagulant activity was studied in vivo by determining the prothrombin time (PT). Compounds 4a (PT = 10.88 ± 0.56 sec) and 4b (13.10 ± 3.56 sec) were the most active and comparable to the reference drug warfarin (7.97 ± 1.93 sec).

Synthesis and In Vivo Evaluation of New Coumarin Conjugates as Potential Indirect-Action Anticoagulants

Quantitative analysis of fructans in functional foods by high-performance anion-exchange chromatography with pulsed amperometric detection

A novel regenerated cellulose (RC) membrane containing cerium oxide (CeO2) nanoparticles is described in detail. In this work, CeO2 nanoparticles with high surface area and mesoporosity were prepared by a modified template-assisted precipitation method. Successful synthesis was achieved using cerium nitrate as a precursor, adjusting the final pH solution to around 11 by ammonium hydroxide and ethylene diamine, and annealing at 550 °C for 3 hours under a protective gas flow. This resulted in a surface area of 55.55 m².g–1 for the nanoparticles. The regenerated cellulose membrane containing CeO2 particles was synthesized by the novel and environmentally friendly method. The catalyst CeO2 and cellulose/CeO2 membrane were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), Electron paramagnetic resonance (EPR), and Brunauer-Emmett-Teller (BET) measurements. The g-value of 2.276 has confirmed the presence of the surface superoxide species of CeO2 nanoparticles in EPR. The photocatalytic activity of the catalyst and the membrane containing the catalyst was evaluated through the degradation of methylene blue under visible light irradiation by UV-VIS measurements. The cellulose/CeO2 membrane degraded 80% of the methylene blue solution in 120 minutes, showing a better photocatalytic activity than the CeO2 catalyst, which degraded approximately 62% in the same period. It has been proven that the RC membrane is not only a good transparent supporting material but also a good adsorption for high-performance of CeO2 catalyst. Copyright © 2022 by Authors, Published by BCREC Group. This is an open access article under the CC BY-SA License (https://creativecommons.org/licenses/by-sa/4.0). 

https://ejournal2.undip.ac.id/index.php/bcrec/article/download/15384/7990

Nguyen Cong Bang

Papers

Synthesis and In Vivo Evaluation of New Coumarin Conjugates as Potential Indirect-Action Anticoagulants

Quantitative analysis of fructans in functional foods by high-performance anion-exchange chromatography with pulsed amperometric detection

Catalytic Dye Oxidation over CeO2 Nanoparticles Supported on Regenerated Cellulose Membrane