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Despite the discovery of many chemotherapeutic drugs that prevent uncontrolled cell division processes in the last century, many studies are still being carried out to develop drugs with higher anticancer efficacy and lower level of side effects. Herein, we designed, synthesized, and characterized six novel coumarin-triazole hybrids, and evaluated for anticancer activity of the one with the highest potential against the breast cancer cell line, MCF-7 and human cervical cancer cell line, human cervical adenocarcinoma (HeLa). Compound 21 which was the coumarin derivative including phenyl substituent with the lowest IC50 value displayed the highest cytotoxicity against the studied cancer cell line. Furthermore, the potential use of poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) prepared by the emulsifying solvent evaporation method as a platform for a drug delivery system was studied on a selected coumarin derivative 21. This coumarin derivative - loaded PLGA NPs were produced with an average size of 225.90 ± 2.96 nm, −16.90 ± 0.85 mV zeta potential, and 4.12 ± 0.90% drug loading capacity. The obtained 21 -loaded PLGA nanoparticles were analyzed spectroscopically and microscopically with FT-IR, UV–vis, and scanning electron microscopy as well as thermogravimetric analysis, Raman, and x-ray diffraction. The in vitro release of 21 from the nanoparticles exhibited a controlled release profile just over one month following a burst release in the initial six hours and in addition to this a total release ratio of %50 and %85 were obtained at pH 7.4 and 5.5, respectively. 21 -loaded PLGA nanoparticles displayed remarkably effective anticancer activity than 21. The IC50 values were determined as IC50 (21 -loaded PLGA nanoparticles): 0.42 ± 0.01 mg ml−1 and IC50 (free 21 molecule): 5.74 ± 3.82 mg ml−1 against MCF-7 cells, and as IC50 (21 -loaded PLGA nanoparticles): 0.77 ± 0.12 mg ml−1 and IC50 (free 21 molecule): 1.32 ± 0.31 mg ml−1 against HeLa cells after the incubation period of 24 h. Our findings indicated that triazole-substituted coumarins may be used as an anticancer agent by integrating them into a polymeric drug delivery system providing improved drug loading and effective controlled drug release. [ABSTRACT FROM AUTHOR]

Numerous physiological processes happening in the human body, including cerebral development and function, require the participation of biometal ions such as iron, copper, and zinc. Their dyshomeostasis may, however, contribute to the onset of Alzheimer's disease (AD) and potentially other neurodegenerative diseases. Chelation of biometal ions is therefore a therapeutic strategy against AD. This review provides a survey of natural and synthetic chelating agents that are or could potentially be used to target the metal hypothesis of AD. Since metal dyshomeostasis is not the only pathological aspect of AD, and the nature of this disorder is very complex and multifactiorial, the most efficient therapeutics should target as many neurotoxic factors as possible. Various coumarin derivatives match this description and apart from being able to chelate metal ions, they exhibit the capacity to inhibit cholinesterases (ChEs) and monoamine oxidase B (MAO-B) while also possessing antioxidant, anti-inflammatory, and numerous other beneficial effects. Compounds based on the coumarin scaffold therefore represent a desirable class of anti-AD therapeutics. [ABSTRACT FROM AUTHOR]

AbstractA new coumarin (1) and a new flavonoid (2) were isolated from the air-dried flower buds of Ochrocarpus longifolius, together with ten known compounds (3–12). The structures of two new compounds were established by 1D and 2D NMR and MS data. In addition, the new compound 2 showed significant proliferation inhibitory activity on Eca-109 and MGC-803 cells. The results of this study may enrich the diversity of compounds from O. longifolius and provide a basis for further research on its natural products and pharmacological activities. [ABSTRACT FROM AUTHOR]

This article discusses the synthesis and characterization of 3-triazinyl-7-aminocoumarins, which are important compounds with various applications. The authors explore different synthetic approaches and find that a C–H/C–H cross-coupling method using heptafluorobutyric acid as a catalyst is a more straightforward and environmentally-friendly approach. They optimize the reaction conditions and identify the best conditions for synthesis. The article also provides detailed information on the physical and chemical properties of various compounds, including their spectroscopic data and yields. Supporting information is available online. [Extracted from the article]

Transition‐metal ions catalyzed intramolecular hydroarylation of aryl alkynoates to construct coumarin skeletons is merited for its step and atom‐economic advantages when compared with other methodologies. The challenge is that the electrophilic cyclization of this reaction requires the strong electrophilic capability of the catalyst, which makes this methodology was seldomly developed after its early explorations. Herein, we report a Lewis acid promoted Pd(II)‐catalyzed intramolecular hydroarylation to construct coumarin and its derivatives; the linkage of Lewis acid to the Pd(II) species through diacetate bridge improved its electrophilic capability, facilitating the hydroarylation reaction happening under the neutral conditions. [ABSTRACT FROM AUTHOR]

This article discusses the development of a visible-light-mediated three-component radical difunctionalization of alkenes, which allows for the synthesis of alkynyl-functionalized organoborons. The researchers optimized the reaction conditions and found that the use of specific reagents and a photocatalyst led to the desired product in good yield. The reaction was found to be chemoselective and had a broad substrate scope. The authors propose a plausible reaction mechanism based on their experimental findings. This method has potential applications in drug discovery and offers a feasible strategy for constructing alkynyl-functionalized organoborons. The text also provides detailed information about the physical and chemical properties of the product. Additionally, the document provides information on the synthesis and characterization of various chemical compounds, including derivatives of chroman and imidazole. The compounds are described in terms of their physical properties and spectroscopic data. Supporting information is available online. [Extracted from the article]

Background: Major bleeding occurs annually in 1%–3% of patients on vitamin K antagonists (VKAs), despite close monitoring. Genetic variants in proteins involved in VKA response may affect this risk. Aim: To determine the association of genetic variants (cytochrome P450 enzymes 2C9 [CYP2C9] and 4F2 [CYP4F2], gamma‐glutamyl carboxylase [GGCX]) with major bleeding in VKA users, separately and combined, including vitamin K epoxide reductase complex subunit‐1 (VKORC1). Methods: A case‐cohort study was established within the BLEEDS cohort, which includes 16,570 patients who initiated VKAs between 2012 and 2014. We selected all 326 major bleeding cases that occurred during 17,613 years of follow‐up and a random subcohort of 978 patients. We determined variants in CYP2C9, CYP4F2, GGCX, VKORC1 and evaluated the interaction between variant genotypes. Hazard ratios for major bleeding with 95% confidence intervals (95% CI) were estimated by weighted Cox regression. Results: Genotype was determined in 256 cases and 783 subcohort members. Phenprocoumon was the most prescribed VKA for both cases and the subcohort (78% and 75%, respectively). Patients with major bleeding were slightly older than subcohort patients. CYP4F2‐TT carriership was associated with a 1.6‐fold (95% CI 0.9–2.8) increased risk of major bleeding compared with CC‐alleles, albeit not statistically significant. For the CYP2C9 and GGCX variants instead, the major bleeding risk was around unity. Carrying at least two variant genotypes in CYP2C9 (poor metabolizer), CYP4F2‐TT, and VKORC1‐AA was associated with a 4.0‐fold (95%CI 1.4–11.4) increased risk, while carriers of both CYP4F2‐TT and VKORC1‐AA had a particularly increased major bleeding risk (hazard ratio 6.7, 95% CI 1.5–29.8) compared with carriers of CC alleles in CYP4F2 and GG in VKORC1. However, the number of major bleeding cases in carriers of multiple variants was few (8 and 5 patients, respectively). Conclusions: CYP4F2 polymorphism was associated with major bleeding, especially in combination with VKORC1 genetic variants. These variants could be considered to further personalize anticoagulant treatment. [ABSTRACT FROM AUTHOR]

A novel metal-free synthesis of 3-substituted isocoumarins through a sequential O-acylation/Wittig reaction has been established. The readily accessible (2-carboxybenzyl)-triphenylphosphonium bromide and diverse chlorides produced various 1H-isochromen-1-one in the presence of triethylamine, employing sequential O-acylation and an intramolecular Wittig reaction of acid anhydride. Reactions using these facile conditions have exhibited high functional group tolerance and excellent yields (up to 90%). Moreover, the fluorescence properties of isocoumarin derivatives were evaluated at the theoretical and experimental levels to determine their potential application in fluorescent materials. These derivatives have good photoluminescence in THF with a large Stokes shift and an absolute fluorescence quantum yield of up to 14%. [ABSTRACT FROM AUTHOR]

In this work, we report on the synthesis and investigation of new hybrid multifunctional iron oxide nanoparticles (IONPs) coated by coumarin-bound copolymer, which combine magneto- or photothermal heating with luminescent thermometry. A series of amphiphilic block copolymers, including Coum-C11-PPhOx27-PMOx59 and Coum-C11-PButOx8-PMOx42 bearing luminescent and photodimerizable coumarin moiety, as well as coumarin-free PPhOx27-PMOx57, were evaluated for their utility as luminescent thermometers and for encapsulating spherical 26 nm IONPs. The obtained IONP@Coum-C11-PPhOx27-PMOx59 nano-objects are perfectly dispersible in water and able to provide macroscopic heating remotely triggered by an alternating current magnetic field (AMF) with a specific absorption rate (SAR) value of 240 W.g−1 or laser irradiation with a photothermal conversion efficiency of η = 68%. On the other hand, they exhibit temperature-dependent emission of coumarin offering the function of luminescent thermometer, which operates in the visible region between 20 °C and 60 °C in water displaying a maximal relative thermal sensitivity (Sr) of 1.53%·°C−1 at 60 °C. [ABSTRACT FROM AUTHOR]

Coumarins represent a diverse class of natural compounds whose importance in pharmaceutical and agri-food sectors has motivated multiple novel synthetic derivatives with broad applicability. The phenolic moiety in 4-hydroxycoumarins underscores their potential to modulate the equilibrium between free radicals and antioxidant species within biological systems. The aim of this work was to assess the antioxidant activity of 18 4-hydroxycoumarin coumarin derivatives, six of which are commercially available and the other 12 were synthesized and chemically characterized and described herein. The 4-hydroxycoumarins were prepared by a two steps synthetic strategy with satisfactory yields. Their antioxidant potential was evaluated through three in vitro methods, two free radical-scavenging assays (DPPH• and ABTS•+) and a metal chelating activity assay. Six synthetic coumarins (4a, 4g, 4h, 4i, 4k, 4l) had a scavenging capacity of DPPH• higher than butylated hydroxytoluene (BHT) (IC50 = 0.58 mmol/L) and compound 4a (4-hydroxy-6-methoxy-2 H-chromen-2-one) with an IC50 = 0.05 mmol/L outperformed both BHT and ascorbic acid (IC50 = 0.06 mmol/L). Nine hydroxycoumarins had a scavenging capacity against ABTS•+ greater (C3, 4a, 4c) or comparable (C1, C2, C4, C6, 4g, 4l) to Trolox (IC50 = 34.34 µmol/L). Meanwhile, the set had a modest ferrous chelation capacity, but most of them (C2, C5, C6, 4a, 4b, 4h, 4i, 4j, 4k, 4l) reached up to more than 20% chelating ability percentage. Collectively, this research work provides valuable structural insights that may determine the scavenging and metal chelating activity of 4-hydroxycoumarins. Notably, substitutions at the C6 position appeared to enhance scavenging potential, while the introduction of electron-withdrawing groups showed promise in augmenting chelation efficiency. [ABSTRACT FROM AUTHOR]

The precise, controllable, and safe application of pesticides can effectively reduce pesticide consumption and minimize chemical pollution at the source. Here, a light‐responsive controlled‐release system with flexible control, precise release, easy recovery, and suitability for future pesticide application in aquatic environments is proposed. The system precisely controls the release of pesticides through a light‐responsive composite nanochannel membrane (CTC@SNM/PET) with reactive coumarin derivatives (CTC) as gating molecules. The prepared nanochannel membrane has an ultrathin thickness of 67.5 nm and well‐ordered vertical nanochannels with a uniform size of 1.9 nm, providing a prerequisite for precise molecular gating and high permeability for mass transport. CTC monomers can realize cycloaddition/cyclocracking and nanochannel closing/opening to control the release of pesticides by controlling 365/254 nm ultraviolet light irradiation. As a proof of concept, the light‐responsive controlled‐release system based on CTC@MSF/PET against Saprolegnia parasitica achieves an inhibition rate of more than 95% and reduces pesticide residues by 56.5% compared to the control group. The proposed membrane system has great application potential to easily enable remote, quantitative, timed, and positioned pesticide application, thereby reducing pesticide residues and providing a prospective approach to reducing environmental and human risks. [ABSTRACT FROM AUTHOR]

This aimed to develop a comprehensive theoretical protocol for examining substitution reaction processes. The researchers used a theoretical quantum-mechanical protocol based on the QM-ORSA approach, which estimates the kinetic parameters of thermodynamically favourable reaction pathways. This theoretical protocol was validated by experimentally investigating substitution mechanisms in two previously synthesised Pd(II) complexes: chlorido-[(3-(1-(2-hydroxypropylamino)ethylidene)chroman-2,4-dione)]palladium(II) (C1) and chlorido-[(3-(1-(2-mercaptoethylamino)-ethylidene)-chroman-2,4dione)]palladium(II) (C2), along with biologically relevant nucleophiles, namely L -cysteine (L -Cys), L -methionine (L -Met), and guanosine-5′-monophosphate (5′-GMP). Reactions were investigated under pseudo-first-order conditions, monitoring nucleophile concentration and temperature changes using stopped-flow UV-vis spectrophotometry. All reactions were conducted under physiological conditions (pH = 7.2) at 37 °C. The reactivity of the studied nucleophiles follows the order: L -Cys > L -Met > 5′-GMP, and the reaction mechanism is associative based on the activation parameters. The experimental and theoretical data showed that C2 is more reactive than C1, confirming that the complexes' structural and electronic properties greatly affect their reactivity with selected nucleophiles. The study's findings have confirmed that the primary interaction occurs with the acid–base species L -Cys, mostly through the involvement of the partially negative sulfur atom (87.2%). On the other hand, C2 has a higher propensity for reacting with L -Cys−, primarily through the partially negative oxygen atom (92.6%). The implementation of this theoretical framework will significantly restrict the utilization of chemical substances, hence facilitating cost reduction and environmental protection. [ABSTRACT FROM AUTHOR]

Hypochlorous acid (HOCl) is widely recognized as a reactive oxygen species of considerable importance in biological systems, and its abnormal metabolism is closely related to various diseases. Therefore, accurately tracking and detecting the concentration levels of HOCl in living organisms hold significant importance in exploring its biological functionalities and related pathological mechanisms. In this work, a coumarin-based fluorescent probe, Cse, containing a selenide group has been developed for fluorescence imaging intracellular and zebrafish HOCl levels. On the basis of the specific oxidation reaction between hypochlorous acid and phenyl selenide, Cse displayed a remarkable fluorescence turn-on response to hypochlorous acid (over 30-fold increase) with a notable Stokes shift (approximately 112 nm), rapid response kinetics (Kobs = 0.389 min−1), and a low detection limit (10.5 nM). Moreover, biological imaging experiments demonstrated that probe Cse enables the visualization of HOCl in real-time through fluorescence imaging techniques, both in living HeLa cells and zebrafish specimens. The successful advancement of this probe provides a novel fluorescence imaging tool to investigate the biological mechanisms associated with diseases related to HOCl. [ABSTRACT FROM AUTHOR]

The document is a contents list for the journal Chemical Communications, published by The Royal Society of Chemistry. It includes articles on various topics such as photocatalytic production of hydrogen peroxide, metal-organic frameworks as solid-state electrolytes for lithium batteries, and the redox noninnocence of a phenothiazine-substituted borane. The journal aims to connect the world with the chemical sciences and invest its profits back into the chemistry community. [Extracted from the article]

The late-stage fluorescent labeling of structurally complex peptides bears immense potential for molecular imaging. Herein, we report on a manganese(I)-catalyzed peptide C–H alkenylation under exceedingly mild conditions with natural fluorophores as coumarin- and chromone-derivatives. The robustness and efficiency of the manganese(I) catalysis regime was reflected by a broad functional group tolerance and low catalyst loading in a resource- and atom-economical fashion. [ABSTRACT FROM AUTHOR]

Hydrazine, a highly toxic compound, demands sensitive and selective detection methods. Building upon our previous studies with pre-coumarin OFF–ON sensors for fluoride anions, we extended our strategy to hydrazine sensing by adapting phenol protecting groups (propionate, levulinate, and γ-bromobutanoate) to our pre-coumarin scaffold. These probes reacted with hydrazine, yielding a fluorescent signal with low micromolar limits of detection. Mechanistic studies revealed that hydrazine deprotection may be outperformed by a retro-Knoevenagel reaction, where hydrazine acts as a nucleophile and a base yielding a fluorescent diimide compound (6,6′-((1E,1′E)-hydrazine-1,2diylidenebis(methaneylylidene))bis(3(diethylamino)phenol, 7). Additionally, our pre-coumarins unexpectedly reacted with primary amines, generating a fluorescent signal corresponding to phenol deprotection followed by cyclization and coumarin formation. The potential of compound 3 as a theranostic Turn-On coumarin precursor was also explored. We propose that its reaction with ALDOA produced a γ-lactam, blocking the catalytic nucleophilic amine in the enzyme's binding site. The cleavage of the ester group in compound 3 induced the formation of fluorescent coumarin 4. This fluorescent signal was proportional to ALDOA concentration, demonstrating the potential of compound 3 for future theranostic studies in vivo. [ABSTRACT FROM AUTHOR]

This article discusses the synthesis of axially chiral bibenzo[g]coumarin derivatives using rhodium-catalyzed oxidative annulation of thiocarbamates. The development of efficient synthetic methods for polycyclic heteroaromatic compounds has been a topic of interest in organic chemistry. The authors describe the synthesis of new binaphthyl-fused chiral bibenzo[g]coumarin derivatives and evaluate their optical properties. The compounds showed fluorescence and circular dichroism characteristics, indicating their potential applications in various fields. The authors also propose a possible reaction mechanism for the synthesis of these derivatives. [Extracted from the article]

The post-column reaction method enables the evaluation of the antiradical capacity of individual components in a mixture by separating the components using HPLC and measuring stable free radical (e.g., DPPH●) scavenging that occurs after the chromatography column. The equipment typically consists of two detectors. The first records signals of the analytes leaving the column. The second records radical scavenging by the analytes, which appears as a negative band. The recorded signals are found on two separate chromatograms, which must be combined to interpret the results. In this study, a single DAD detector was used behind the post-column reactor, enabling the simultaneous recording of the analyte bands and negative signals, indicating radical scavenging. The objective of this study was to evaluate the antiradical capacity of key compounds found in two herbal raw materials used in traditional Chinese medicine. Saposhnikovia divaricata roots contain phenolic acids, chromones, and furanocoumarins. Chlorogenic acid, rosmarinic acid, and imperatorin demonstrated strong radical scavenging, while prim-O-glucoslocimifugin showed a weaker response, both in standards and in root extracts. However, scavenging was not observed for cimifugin and 4′-O-β-D-glucosyl-5-O-methylvisamminol. Astragalus mongholicus roots contain astragalosides I-IV (triterpene saponins). None of these showed DPPH● scavenging. Furthermore, additional signals were observed, indicating the presence of unidentified radical scavenging compounds. [ABSTRACT FROM AUTHOR]

This article provides a comprehensive overview of the synthesis and modification of organic fluorophores, which are organic compounds that emit light when excited. It discusses various synthetic reactions used to create these fluorescent molecules, with a focus on transition-metal-catalyzed C–H activation reactions. The article categorizes recent C–H activation reactions and evaluates their advantages and limitations. This information is valuable for researchers and readers interested in the field of organic fluorophores. The document also includes biographical information about the authors, Dr. Tapasi Chand and Dr. Manmohan Kapur. [Extracted from the article]

In this study, several fused heterocyclic systems involving tetrahydrobenzopyrans 7a-i and tetrahydrobenzopyridines 9a-i were synthesized. The reactions proceed via a multicomponent reaction of different aromatic aldehydes, cyanoacetanilide derivatives, and cyclohexane-1,3-dione. All the produced compounds were tested for their anticancer activity by using six cancer cell lines such as A549, HT-29, MKN-45, U87MG, SMMC- 7721 and H460 utilizing foretinib as the positive control and the standard MTT assay in vitro. The results indicated that many synthesized derivatives were the most potent towards all the cancer cell lines used, six compounds 7e, 7f, 9b, 9d, 9e, and 9g showed the highest potency. The results obtained in this work enhance further investigations in the future. [ABSTRACT FROM AUTHOR]

Coumarins, a subgroup of colorless and crystalline oxygenated heterocyclic compounds originally discovered in the plant Dipteryx odorata, were the subject of a recent study investigating their quantitative structure–activity relationship (QSAR) in cancer pharmacotherapy. This study utilized graph theoretical molecular descriptors, also known as topological indices, as a numerical representation method for the chemical structures embedded in molecular graphs. These descriptors, derived from molecular graphs, play a pivotal role in quantitative structure–property relationship (QSPR) analysis. In this paper, intercorrelation between the Balban index, connective eccentric index, eccentricity connectivity index, harmonic index, hyper Zagreb index, first path Zagreb index, second path Zagreb index, Randic index, sum connectivity index, graph energy and Laplacian energy is studied on the set of molecular graphs of coumarins. It is found that the pairs of degree-based indices are highly intercorrelated. The use of these molecular descriptors in structure–boiling point modeling was analyzed. Finally, the curve-linear regression between considered molecular descriptors with physicochemical properties of coumarins and coumarin-related compounds is obtained. Some of the coumarin-related anti-cancer compounds considered in this study [ABSTRACT FROM AUTHOR]

A catalyst-, oxidant-free and green synthetic route for direct access to a series of novel imidazopyridine-linked coumarins has been devised through tandem C(sp2)–H functionalization/decarboxylation reaction in ethyl acetate as a sustainable medium. Moreover, the utilities of ensured products in further organic synthesis were conducted by Suzuki–Miyaura and Sonogashira cross-coupling reactions. The fluorescence characteristics of the produced molecules are appropriate, and the synthesized scaffolds could promisingly garner future attention in clinical diagnostics and bioimaging research. [ABSTRACT FROM AUTHOR]

A biocompatible fluorescence sensor for cysteine detection receives wide appreciation recently, because of its importance in the medical field. Functionalized graphene quantum dots (GQDs) are recently emerging biocompatible quantum dots, which are considered as suitable candidates for biomolecule detection. Motivated by this concept, here we have developed a versatile fluorescent probe based on 3‐aminocoumarin (AMC) functionalized GQDs for the detection of cysteine (Cys). Modification on GQD with AMC resulted in a stable fluorescent probe with an enhancement in quantum yield of about 84% and 40 nm redshift in emission peak compared with bare GQD. The modified GQD is then used for the sensitive and selective detection of cysteine in aqueous media. The detection of Cys within the linear range of 50 nM to 1.5 μM was achieved with a detection limit (LOD) of 0.86 nM. Here, the AMC‐GQD exhibit a turn‐off fluorescence sensing behavior. The quenching mechanism was also explored. The sensing process follows dynamic quenching mechanism, which is attributed to the photoinduced charge transfer from AMC‐GQD to Cys. The Stern–Volmer plot, energy‐level alignment obtained from cyclic voltammetry measurements and density functional theory predictions give a valid proof for this. Furthermore, the sensor was applied efficiently to the determination of Cys in real water samples. [ABSTRACT FROM AUTHOR]

Copper-catalyzed azide–alkyne cycloaddition click (CuAAC) reaction is widely used to synthesize drug candidates and other biomolecule classes. Homogeneous catalysts, which consist of copper coordinated to a ligand framework, have been optimized for high yield and specificity of the CuAAC reaction, but CuAAC reaction with these catalysts requires the addition of a reducing agent and basic conditions, which can complicate some of the desired syntheses. Additionally, removing copper from the synthesized CuAAC-containing biomolecule is necessary for biological applications but inconvenient and requires additional purification steps. We describe here the design and synthesis of a PNN-type pincer ligand complex with copper (I) that stabilizes the copper (I) and, therefore, can act as a CuAAC catalyst without a reducing agent and base under physiologically relevant conditions. This complex was immobilized on two types of resin, and one of the immobilized catalyst forms worked well under aqueous physiological conditions. Minimal copper leaching was observed from the immobilized catalyst, which allowed its use in multiple reaction cycles without the addition of any reducing agent or base and without recharging with copper ion. The mechanism of the catalytic cycle was rationalized by density functional theory (DFT). This catalyst's utility was demonstrated by synthesizing coumarin derivatives of small molecules such as ferrocene and sugar. [ABSTRACT FROM AUTHOR]

In the frame of a systematic study on the sequestering ability of natural antioxidants towards metal cations, here the complexation of coumarin-3-carboxilic acid (HCCA) with Pb(II) and the overall stability constants of the resulting complexes, at 37 °C and in 0.16 M NaClO4, are discussed. Reaction of Pb(ClO4)2 with HCCA in an aqueous medium at a pH range from 2 to 6 and various ratios (1:1–1:10) yielded the Pb–CCA complexes, which were characterized spectrometrically by laser desorption ionization mass spectrometry (LD-MS). LD-MS has provided the composition and structure of Pb–CCA species according to the speciation model proposed on the basis of the potentiometric data. The graphic representation of the complex's concentration curves is given by the distribution diagram, which provides a whole depiction of the species present in the solution at the selected pH ranges. [ABSTRACT FROM AUTHOR]

Cu(II) Complex of tetradentate Schiff-base supported on silica [Cu(II) Schiffbase@-SiO2] catalyzed reactions of aryl aldehydes with carbonyl compounds (dimedon/4-hydroxy coumarin/1,3-cyclohexadion) and malononitrile in aqueous media (H2O:EtOH) to preparation of benzo[b]pyrans and 3,4-dihydropyrano[c] chromanes. Also, using this nanocatalyst, 2-(5-substituted phenyl)furan2-carboxaldehyde derivatives with carbonyl compounds (dimedon/4-hydroxy coumarin/1,3-cyclohexadion) and malononitrile gave novel tetrahydrobenzo [b]pyran and 3,4-dihydropyrano[c]chromane derivatives in high yields in H2O: EtOH under reflux conditions. The key advantages of this catalytic systems are the formation of novel products, high yields (78%–93%), short reaction time, broad substrate scope, environmentally friendly reaction conditions and also, without need to column chromatography for purification. Furthermore, the nanocatalyst can be reused six times without losing catalytic activity. [ABSTRACT FROM AUTHOR]

Objective: The phytochemical study of the extract of hexane, dichlorometane, and methanol from the aerial parts of Hinterhubera imbricate collected in the State of Mérida, Venezuela was performed in this research. Methods: The purification of the extracts and isolation of the secondary metabolites was done through column chromatography. Compounds were identified and characterized by gas chromatography coupled to mass spectrometry, infrared spectroscopy and nuclear magnetic resonance analysis. Antibacterial activity was evaluated in vitro using the disk agar diffusion method against international reference strains of Staphylococcus aureus, Escherichia coli, Enterococcus faecalis, Klebsiella pneumoniae and Pseudomonas aeruginosa. Antioxidant activity was determined in vitro through the 2,2-diphenyl-1-picrylhidrazyl free radical method. Results: Phytochemical screening reports the presence in hexane and dichloromethane extracts of leaves-stems of triterpenes and sterols, and in methanol extracts of leaves, stems and flowers; sterols, phenolic compounds, flavonoids and coumarins. Four compounds were isolated and identified as 7-hydroxy-6-methoxycoumarin, friedelone, friedelan-3-ol and ursolic acid. All extracts showed activity against S. aureus and K. pneumoniae at a concentration of 1000 µg/mL, being the most active the methanol extracts (leaves-stems and flowers) with a minimum inhibitory concentration of 250 and 125 µg/mL, respectively. The antioxidant activity was moderate, being the median effective concentration of 12.9 and 8.3 µg/mL, for the methanol extract of leaves-stems and flowers. Conclusion: The aerial parts of Hinterhubera imbricate contain secondary metabolites with antibacterial and antioxidant activity, being this species a source of biologically active substances. [ABSTRACT FROM AUTHOR]

Yuliani N, Rachmadi R, Oksari AA, Wanda IF. 2024. Antioxidant activity of invasive species Solanum jamaicense. Nusantara Bioscience 16: 54-61. Solanum jamaicense Mill. belongs to the Solanaceae family and is categorized as an invasive species. The leaves of S. jamaicense own some of these compounds, which are known to contain several compounds, including phenolics, coumarins, and flavonoids, which have the potential to be a source of antioxidants. This study aims to determine the content of phytochemical compounds and antioxidant activity of the leaves of S. jamaicense. Phytochemical testing includes tests for alkaloids, flavonoids, saponins, tannins, steroids, and terpenoids. The total phenolic content was tested using tannic acid as a comparison by spectrophotometry. They tested the antioxidant activity of S. jamaicense leaf extract by using spectrophotometric method. The antioxidant activity of the extract is expressed in the value of 50% Inhibition Concentration (IC50). Based on the results of the phytochemical test, the ethanol extract of S. jamaicense leaves contains alkaloids, flavonoids, tannins, saponins, and steroids. The research showed that the total phenolic content was 59.953 mg.g-1 of the extract, and the antioxidant activity was intense, with an IC50 value of 10.41 mg.L-1 (active). S. jamaicense leaves ethanol extract has the potential as a source of natural antioxidants. [ABSTRACT FROM AUTHOR]

The constant need for high‐performance aniline‐ or phenol‐based fluorophores suitable for the construction of activity‐based fluorescent probes, led us to study both synthesis and photophysics of C3‐N‐methylpyridinium‐4‐yl substituted 7‐(dialkylamino)/7‐hydroxycoumarins. Indeed, in the field of photoactive organic molecules, the positively charged N‐alkylpyridinium‐4‐yl groups are often used as acceptor units to dramatically impact spectral features through promoting intramolecular charge transfer (ICT) processes. They are also known as effective water‐solubilizing and mitochondria targeting moieties. The poor fluorescence efficiency of cationic 7‐hydroxycoumarin derivatives in aqueous physiological conditions was highlighted and rationalized by the predominance of a neutral quinonoid form in such buffer medium. The ability of the excited singlet state (S1) of this neutral species to undergo intersystem crossing (ISC) to triplet state (T1) was partly supported by phosphorescence measurements of singlet oxygen. We also took advantage of green‐emissive properties of 7‐(diethylamino)‐3‐(N‐methylpyridinium‐4‐yl)coumarin to successfully design and validate a novel small‐molecule fluorescent probe for the detection of alkaline phosphatase (ALP), based on the "covalent‐assembly" principle. A practical use of ortho‐formylated 7‐hydroxy‐3‐(N‐methylpyridinium‐4‐yl)coumarin was next considered with the synthesis of a Fe(III)‐salen complex whose the potential as a "molecular disassembly" probe for fluorogenic sensing of pyrophosphate (PPi) anion was assessed. [ABSTRACT FROM AUTHOR]

Eight novel compounds incorporating chalcone and coumarin features, namely chalcone‐coumarin‐ hybrid molecules, were designed, synthetized, and evaluated for their activity against human colorectal carcinoma SW480 cell line. According to the results observed, the hybrid with a 2,3‐dimetoxysubstitution pattern displayed the highest activity at the conditions evaluated, with an IC50 value of 25.18±1.12 μM, being even more active than the reference drug (5‐fluorouracil) and the parental compound (7‐methylcoumarin). In addition, this hybrid compound exhibited significant antiproliferative activity in a time‐ and concentration dependent way, suggesting rather a cytostatic or cytotoxic effect. Moreover, a theoretical drug‐like/pharmacokinetics/toxicological study suggested that the most promising hybrid would have a great chance to advance to further preclinical studies as anti‐cancer therapeutic candidate for oral oncological management. Our study evidently identified the potency of chalcone‐coumarin conjugates, particularly the 2,3‐dimetoxysubstituited molecule to be a prototype drug for further investigations toward novel therapeutics treatments of colorectal cancer. [ABSTRACT FROM AUTHOR]

Quaternary N‐aryl‐DABCO salts were introduced for the first time as a highly selective sensing platform for thiols and selenols. By employing this platform, a highly sensitive coumarin based "off‐on" fluorescent probe was designed and synthesized. The probe possesses a good solubility in water, low background fluorescence, and, most importantly, demonstrates high selectivity to aryl thiols and selenols over their aliphatic counterparts and other common nucleophiles. A dramatic increase in fluorescence intensity is achieved through the selective cleavage of the quaternized DABCO‐ring, yielding a piperazine derivatives with a high fluorescence quantum yield (~72 %). Moreover, stability of the probe to the most used reducing agents DTT and TCEP was demonstrated. The limits of detection for p‐thiocresol and phenyl selenide were evaluated to be 22 nM and 6 nM, respectively. [ABSTRACT FROM AUTHOR]

Coumarins are heterocycles of great interest in the development of valuable active structures in chemistry and biological domains. The ability of coumarins to inhibit biofilm formation of Gram positive bacterium (Staphylococcus aureus), Gram negative bacterium (Escherichia coli) as well as the methicillin-resistant S. aureus (MRSA) has been previously described. In the present work, new hybrid coumarin-heterocycles have been synthesized via the reaction of coumarin-6-sulfonyl chloride and 6-aminocoumarin with different small heterocycle moieties. The biological efficacy of the new compounds was evaluated towards their ability to inhibit biofilm formation and their anti-inflammatory properties. The antimicrobial activities of the newly synthesized compounds were tested against Gram positive bacterium (S. aureus ATCC 6538), Gram negative bacterium (E. coli ATCC 25922), yeast (Candida albicans ATCC 10231) and the fungus (Aspergillus niger NRRL-A326). Compounds 4d, 4e, 4f, 6a and 9 showed significant MIC and MBC values against S. aureus, E. coli, C. albicans, and methicillin-resistant S. aureus (MRSA) with especial incidence on compound 9 which surpasses all the other compounds giving MIC and MBC values of (4.88 and 9.76 µg/mL for S. aureus), (78.13 and 312.5 µg/mL for E. coli), (9.77 and 78.13 µg/mL for C. albicans), and (39.06 and 76.7 µg/mL for MRSA), respectively. With reference to the antibiofilm activity, compound 9 exhibited potent antibiofilm activity with IC50 of 60, 133.32, and 19.67 µg/mL against S. aureus, E. coli, and MRSA, (respectively) considering the reference drug (neomycin). Out of all studied compounds, the anti-inflammatory results indicated that compound 4d effectively inhibited nitric oxide production in lipopolysaccharide-(LPS-) stimulated RAW264.7 macrophage cells, giving NO% inhibition of 70% compared to Sulindac (55.2%) [ABSTRACT FROM AUTHOR]

The present work represents a novel methodology for the selective arylation of coumarin‐3‐carboxylates with arylboronic acids via a photochemical route, marking the first‐ever attempt for the direct alkenyl C−H arylation using rose bengal as a photocatalyst, which is a readily available and cost‐effective alternative to transition metal catalysis. The reaction proceeds smoothly in MeOH/H2O solvent media in the presence of radical initiator affording the arylated products in good yields (60–80 %). The reaction parameters such as visible light, radical initiator, oxidant, anhydrous solvent, and inert atmosphere play a crucial role for the success of this methodology. The substituents present on the substrate show a significant effect on the conversion. This study provides a valuable contribution to the field of organic synthesis offering a new and efficient approach to the arylation of coumarin‐3‐carboxylic acid esters with a broad substrate scope and high functional group tolerance. It is a versatile method and provides a direct access to biologically relevant 4‐arylcoumarin‐3‐carboxylates. [ABSTRACT FROM AUTHOR]

The fungus Xylaria sp. Z184, harvested from the leaves of Fallopia convolvulus (L.) Á. Löve, has been isolated for the first time. Chemical investigation on the methanol extract of the culture broth of the titles strain led to the discovery of three new pyranone derivatives, called fallopiaxylaresters A–C (1–3), and a new bisabolane-type sesquiterpenoid, named fallopiaxylarol A (4), along with the first complete set of spectroscopic data for the previously reported pestalotiopyrone M (5). Known pyranone derivatives (6–11), sesquiterpenoids (12–14), isocoumarin derivatives (15–17), and an aromatic allenic ether (18) were also co-isolated in this study. All new structures were elucidated by the interpretation of HRESIMS, 1D, 2D NMR spectroscopy, and quantum chemical computation approach. The in vitro antimicrobial, anti-inflammatory, and α-glucosidase-inhibitory activities of the selected compounds and the crude extract were evaluated. The extract was shown to inhibit nitric oxide (NO) production induced by lipopolysaccharide (LPS) in murine RAW264.7 macrophage cells, with an inhibition rate of 77.28 ± 0.82% at a concentration of 50 μg/mL. The compounds 5, 7, and 8 displayed weak antibacterial activity against Staphylococcus areus subsp. aureus at a concentration of 100 μM. [ABSTRACT FROM AUTHOR]

Comprehensive Summary Ten novel isocoumarins, including four pairs of enantiomers, were isolated from Artemisia dubia var. subdigitata (Asteraceae). Compounds 1, 2 and 3a/3b possessed a unique 6/6/6‐tricyclic system comprising an unusual 1‐(2‐methylcyclohexyl) propan‐1‐one moiety fused with isocoumarin core skeleton. Compounds 4a/4b were characterized as an unexpected 2,5‐dimethylcyclohexan‐1‐one scaffold, and compounds 5a/5b and 6a/6b were rare 1,2‐seco‐isocoumarin. Their structures and absolute configurations were elucidated through spectroscopic data, X‐ray crystallography, ECD and NMR calculations with DP4+ analyses. Plausible biosynthetic pathways were proposed from the naturally occurring isocoumarin. Network pharmacological analysis suggested that the targets of compound 1 were significantly enriched in the cell cycle and PI3K‐Akt signaling pathway. The molecular docking revealed that compound 1 had high binding affinity with CDK2 (total score: 6.8717). Furthermore, compounds 1 and 2 exhibited inhibitory activity on three human hepatoma cell lines, with inhibitory ratios of 85.1% and 84.5% (HepG2), 88.2% and 87.3% (Huh7), and 69.2% and 69.1% (SK‐Hep‐1) at 200 μmol·L–1, respectively. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The tyrosinase enzyme has a vital role in the browning of vegetables and fruits and the biosynthesis of melanin. In this work, we synthesized a diverse library of coumarin–triazole hybrids, and these compounds were characterized by using suitable analytical techniques. Our research work extends beyond the synthetic effort to explore the therapeutic potential of these compounds. We put the synthesized compounds through meticulous in vitro screening against the tyrosinase enzyme, and these coumarin derivatives evinced good IC50 values in the range of 0.339 ± 0.25 µM to 14.06 ± 0.92 µM. In the library of synthesized compounds, six compounds were found to be more potent than standard ascorbic acid (IC50 = 11.5 ± 1.00), and among them, 17e and 17f, being the most active, exhibited remarkable anti-tyrosinase potential, with IC50 values of 0.339 ± 0.25 μM and 3.148 ± 0.23 μM, respectively. Furthermore, an in silico modeling study was carried out to determine the key interactions of these compounds with the tyrosinase protein (PDB ID: 2Y9X) and thus to authenticate our experimental findings. The quantitative SAR studies exhibited a good correlation between the synthesized derivatives of coumarin and their anti-tyrosinase activity. The docking studies verified the experimental results, and ligand 17e showed good interaction with the core residues of tyrosinase. This study not only expands the field of coumarin–triazole hybrid synthesis but also provides valuable insights for the development of novel tyrosinase inhibitors. [ABSTRACT FROM AUTHOR]

Different methods were used to extract C-phycocyanin from Arthrospira platensis, alone or in synergy (freezing, incubation, ultrasounds, deep eutectic solvents). Freezing or Freeze-drying spirulina allows a highly facilitated rupture of the cell membranes. Incubation in water allows then a quick release of C-PC and other phycobiliproteins at 45 °C (2 h) while it takes less than 8 h at 35 °C and 25–30 h at ambient temperature. In addition to microscopic observation, the evolution of solutes concentration with incubation time confirms that hydrosoluble pigments are first preferentially released relatively to chlorophyll which requires deeper collapse of the spirulina cells. Use of ultrasounds allows an extraction of the spirulina content in 15 min of treatment with a high C-PC extraction yield (> 200 mg/g) and good protein purity (around 0.7). Ethyl acetate, ethanol and a mixture of these solvents give good extraction yields of chlorophyll (around 21 mg/g). C-PC extraction yield is yet then decreased due to a denaturation of the hydrated pigment. Fructose can be used to prevent denaturation by both organic solvent and freezing/freeze-drying. The use of deep-eutectic solvents is not recommended here as no better yield or selectivity are achieved compared to extraction in buffered water. [ABSTRACT FROM AUTHOR]

BACKGROUND: Fig (Ficus carica L.) fruit is consumed worldwide as a functional food. It contains phytochemicals that have been related to health benefits. However, the characteristic chemicals remain unclear. In this work, phytochemicals were prepared from figus by ultrasound‐assisted extraction under optimized conditions. The chemical composition of fig fruit and leaves was characterized by ultra‐high performance liquid chromatography‐tandem mass spectrometry (UPLC‐MS/MS). RESULTS: One hundred and fifty‐seven compounds were identified, including 58 flavonoids, 29 coumarins, 19 acids, 15 terpenoids, 11 alkaloids, and 25 other compounds. The mass spectrum (MS) fragmentation pathways of representative chemicals were elucidated. Flavonoid glycosides and prenylated flavonoids were mainly present in fig fruit, whereas coumarins were abundant in leaves. Both fig fruit and leaf extracts showed good cellular antioxidant activity. CONCLUSION: The full phytochemical profile of fig was revealed by UPLC‐MS/MS. Prenylated flavonoids and prenylated coumarins were the characteristic phytochemicals. These data provided useful information for the extensive utilization of fig fruit in functional food. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Comprehensive Summary An asymmetric isomerization/intramolecular coupling reaction of allylic alcohols to synthesize chiral dihydrocoumarins was successfully accomplished through ruthenium catalysis. This method demonstrates a wide substrate applicability, excellent tolerance for various functional groups, and good enantioselectivities (up to 90% ee). It provides a convenient pathway to produce a diverse range of structurally distinct chiral dihydrocoumarins in good efficiency. [ABSTRACT FROM AUTHOR]

α-Glucosidase inhibitors have emerged as crucial agents in the management of type 2 diabetes mellitus. In the present study, a new series of coumarin-linked 2-phenylbenzimidazole derivatives 5a–m was designed, synthesized, and evaluated as anti-α-glucosidase agents. Among these derivatives, compound 5k (IC50 = 10.8 µM) exhibited a significant inhibitory activity in comparison to the positive control acarbose (IC50 = 750.0 µM). Through kinetic analysis, it was revealed that compound 5k exhibited a competitive inhibition pattern against α-glucosidase. To gain insights into the interactions between the title compounds and α-glucosidase molecular docking was employed. The obtained results highlighted crucial interactions that contribute to the inhibitory activities of the compounds against α-glucosidase. These derivatives show immense potential as promising starting points for developing novel α-glucosidase inhibitors. [ABSTRACT FROM AUTHOR]

A substrate‐induced synthesis of coumarin‐fused quinolinones is achieved from 4‐(phenylamino)‐2H‐chromen‐2‐ones using N‐alkyl amines as the solvent and a carbon source under air conditions without any catalysts in one pot. This protocol highlights the special roles of 4‐(phenylamino)‐2H‐chromen‐2‐ones which were not only used as reactants but also as an internal oxidant selectively activated N‐α‐C(sp3)−H bond. This reaction features catalyst‐free, broad substrate scopes (N‐alkyl amines 27 examples and quinolinones 24 examples), operationally simple for the one‐step synthesis, and recovery and recycling of the solvent. [ABSTRACT FROM AUTHOR]

SARS-CoV, an RNA virus, is contagious and displays a remarkable degree of adaptability, resulting in intricate disease presentations marked by frequent genetic mutations that can ultimately give rise to drug resistance. Targeting its viral replication cycle could be a potential therapeutic option to counter its viral growth in the human body leading to the severe infectious stage. The Mpro of SARS-CoV-2 is a promising target for therapeutic development as it is crucial for viral transcription and replication. The derivatives of β-diketone and coumarin have already been reported for their antiviral potential and, thus, are considered as a potential scaffold in the current study for the computational design of potential analogs for targeting the viral replication of SARS-CoV-2. In our study, we used novel diketone-hinged coumarin derivatives against the SARS-CoV-2 MPro to develop a broad-spectrum antiviral agent targeting SARS-CoV-2. Through an analysis of pharmacokinetics and docking studies, we identified a list of the top 10 compounds that demonstrated effectiveness in inhibiting the SARS-CoV-2 MPro virus. On the basis of the pharmacokinetics and docking analyses, the top 5 novel coumarin analogs were synthesized and characterized. The thermodynamic stability of compounds KS82 and KS94 was confirmed by their molecular dynamics, and the stability of the simulated system indicated their inhibitory nature. Molecules KS82 and KS94 were further evaluated for their anti-viral potential using Vero E6 cells followed by RT-PCR assay against SARS-CoV-2. The test compound KS82 was the most active with the potential to inhibit SARS-CoV-2 replication in Vero E6 cells. These data indicate that KS82 prevents the attack of the virus and emerges as the primary candidate with promising antiviral properties. [ABSTRACT FROM AUTHOR]

This article explores the use of copper complexes as catalysts for radical reactions in organic synthesis. It emphasizes the importance of metal-catalyzed processes in drug development and highlights copper's suitability as a catalyst due to its low cost and availability. The role of ligands in stabilizing copper complexes and influencing their reactivity is also discussed. The authors specifically focus on copper-catalyzed radical cross-coupling reactions and direct alkylation of electron-rich heteroarenes. The article provides detailed information on reaction mechanisms and the broad scope and efficiency of these reactions. Additionally, the authors explore the use of copper complexes in photoinduced radical reactions as an alternative to traditional photoredox catalysts. The challenges and future prospects of copper catalysis in radical chemistry are also addressed, with an emphasis on the advantages of using copper complexes and their potential for developing new radical reactions and processes. [Extracted from the article]

SUMMARY: Plant roots release phytochemicals into the soil environment to influence nutrient availability and uptake. Arabidopsis thaliana roots release phenylpropanoid coumarins in response to iron (Fe) deficiency, likely to enhance Fe uptake and improve plant health. This response requires sufficient phosphorus (P) in the root environment. Nonetheless, the regulatory interplay influencing coumarin production under varying availabilities of Fe and P is not known. Through genome‐wide association studies, we have pinpointed the influence of the ABC transporter G family member, PDR9, on coumarin accumulation and trafficking (homeostasis) under combined Fe and P deficiency. We show that genetic variation in the promoter of PDR9 regulates its expression in a manner associated with coumarin production. Furthermore, we find that MYB63 transcription factor controls dedicated coumarin production by regulating both COUMARIN SYNTHASE (COSY) and FERULOYL‐CoA 6′‐HYDROXYLASE 1 (F6′H1) expression while orchestrating secretion through PDR9 genes under Fe and P combined deficiency. This integrated approach illuminates the intricate connections between nutrient signaling pathways in coumarin response mechanisms. Significance Statement: Plant roots release phenylpropanoid coumarins in response to iron deficiency, potentially enhancing iron uptake. Influenced by phosphorus levels, the regulatory dynamics of coumarin biosynthesis and transport are unknown. Our studies reveal the ABC transporter G family member, PDR9, influences coumarin homeostasis under combined iron and phosphorus deficiency. Genetic variations in PDR9's promoter control its expression, impacting coumarin secretion. The MYB63 transcription factor orchestrates coumarin biosynthesis, linking nutrient signaling pathways in coumarins response mechanisms. [ABSTRACT FROM AUTHOR]

Brønsted acid mediated [3+2] cycloaddition of coumarin‐based enamines with 3‐ylidene oxindoles generated in situ from 3‐hydroxy‐3‐aroylmethyl oxindoles enabled the synthesis of polyheterocyclic compounds with a pyrrolocoumarin core structure in a highly regioselective manner. The synthetic procedure is highly efficient and metal‐free, and no chromatographic purification of the products is required. The chromenopyrrole derivatives bearing an oxindole moiety formed as rapidly interconverting rotamers. [ABSTRACT FROM AUTHOR]

Real-time monitoring of biocatalytic-based processes is significantly improved and simplified when they can be visualized. Visual monitoring can be achieved by integrating a fluorescent unit with the biocatalyst. Herein, we outline the design strategies of fluorescent probes for monitoring biocatalysis: (1) probes for monitoring biocatalytic transfer: γ-glutamine is linked to the fluorophore as both a recognition group and for intramolecular charge transfer (ICT) inhibition; the probe is initially in an off state and is activated via the transfer of the γ-glutamine group and the release of the free amino group, which results in restoration of the "Donor–π–Acceptor" (D–π–A) system and fluorescence recovery. (2) Probes for monitoring biocatalytic oxidation: a propylamine is connected to the fluorophore as a recognition group, which cages the hydroxyl group, leading to the inhibition of ICT; propylamine is oxidized and subsequently β-elimination occurs, resulting in exposure of the hydroxyl group and fluorescence recovery. (3) Probes for monitoring biocatalytic reduction: a nitro group attached to a fluorophore as a fluorescence quenching group, this is converted to an amino group by catalytic reduction, resulting in fluorescence recovery. (4) Probes for monitoring biocatalytic hydrolysis: β- D -galactopyranoside or phosphate acts as a recognition group attached to hydroxyl groups of the fluorophore; the subsequent biocatalytic hydrolysis reaction releases the hydroxyl group resulting in fluorescence recovery. Following these 4 mechanisms, fluorophores including cyanine, coumarin, rhodamine, and Nile-red, have been used to develop systems for monitoring biocatalytic reactions. We anticipate that these strategies will result in systems able to rapidly diagnose and facilitate the treatment of serious diseases. [ABSTRACT FROM AUTHOR]

New coumarin derivatives were designed using a 2-(2-oxo-2H-chromen-4-yl)acetic acid scaffold conjugated with amino acid esters or tyramine. The anti-tyrosinase and anti-lipid peroxidation activities of the synthesized compounds were investigated. Coumarin derivatives 7,9, 11–13, 15–18 showed strong anti-lipid peroxidation activity. Compound 13 exhibited uncompetitive tyrosinase inhibitory activity with an IC50 value of 68.86 µM. Compound 14 (% activity = 123.41) showed stronger tyrosinase activating activity than 8-methoxypsolaren (8-MOP, % activity = 109.46). In silico studies revealed different poses between the inhibitors and activators near the tyrosinase catalytic site. Compounds 13 (25–50 μM) and 14 (25–100 μM) did not show cytotoxicity against B16F10 cells. In contrast to the tyrosinase inhibition assay, compound 13 (50 μM) suppressed melanogenesis in B16F10 cells with two times higher potency than KA (100 μM). Compound 14 at 100 μM showed melanogenesis enhancement in B16F10 cells in a dose-dependent manner, however, inferior to the 8-MOP. Based on the findings, compound 13 and 14 offer potential for development as skin-lightening agents and vitiligo therapy agents, respectively. [ABSTRACT FROM AUTHOR]

This comprehensive review, covering 2021-2023, explores the multifaceted chemical and pharmacological potential of coumarins, emphasizing their significance as versatile natural derivatives in medicinal chemistry. The synthesis and functionalization of coumarins have advanced with innovative strategies. This enabled the incorporation of diverse functional fragments or the construction of supplementary cyclic architectures, thereby the biological and physico-chemical properties of the compounds obtained were enhanced. The unique chemical structure of coumarine facilitates binding to various targets through hydrophobic interactions pi-stacking, hydrogen bonding, and dipole-dipole interactions. Therefore, this important scaffold exhibits promising applications in uncountable fields of medicinal chemistry (e.g., neurodegenerative diseases, cancer, inflammation). [ABSTRACT FROM AUTHOR]