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Coumarin derivatives are one of the naturally occurring bioactive molecule. Dihydropyrano coumarins are one of the medicinally important derivatives of coumarin which have been reported to exhibit various bioactivity. However, there are no reports on their antihyperglycemic activities. Herein, we report their antihyperglycemic potential through α-Amylase inhibition. In this study, a series of 24 derivatives of dihydropyrano coumarins was synthesized and studied for alpha-Amylase inhibitory activity. All the derivatives of dihydropyrano coumarins (4a-x) were screened via molecular docking studies against human pancreatic alpha-Amylase (PDB id: 2QV4) followed by DNS assay to check their α-Amylase inhibitory potential. Six derivatives with o-chloro(4b), o-nitro(4c), p-nitro(4o), p-cyano(4q), p-allyloxy(4t) and m, p-dimethoxy(4v) displayed best binding with the α-Amylase enzyme via H-bond and Pi-alkyl interactions. Also, their physicochemical parameters revealed their drug likeliness. Further through DNS assay, minimal inhibitory concentration, i.e., IC50 values of these six derivatives were calculated. All the six derivatives possess IC50 values in the range 5.67 ± 0.02 to 8.92 ± 0.64 µM comparable to standard acarbose (0.85 ± 0.01 µM). Further DFT analysis gave a comparative study of band gap energy of most potent compound 4o with that of standard acarbose. [ABSTRACT FROM AUTHOR]

Acarbose, miglitol and voglibose are α-glucosidase enzyme inhibitors that are clinically used to treat type-II diabetes mellitus. However, they are also associated with several adverse side effects. In this study, a series of sulfonamide-substituted coumarin was synthesised in a three-step reaction from precursor, 2-oxo-2H-chromene-3-carboxylic acid. The structure of all synthesised compounds was confirmed using NMR, FTIR and LCMS analysis and found to be in good agreement with the calculated values. Synthesised coumarin derivatives were screened for their in vitro α-glucosidase inhibitory activity. Besides compound 8, 15 compounds demonstrated good to excellent inhibitory activity with the IC50 values ranging from 40.6 to 2021 µM as compared to acarbose (IC50 = 3410 ± 1.54 µM). A structure–activity relationship was established to form correlation of the substituents effect with inhibitory activity. It was found that chlorine substituent played an important role in the activity compared to other halogen substituents. Derivatives showing inhibition activity were subjected to docking studies to identify the binding modes contributing towards the inhibition activity. [ABSTRACT FROM AUTHOR]

Background/Objectives: Gardeniae Fructus (GF) has been widely used as both food and medicinal purposes for thousands of years, but their antioxidant properties and potential metabolite biomarkers remain unclear. Methods: The purposes of this study were to examine antioxidant activities of 21 GF varieties from different geographical origins in China and identify potential biomarkers of antioxidant properties using an untargeted LC–MS-based metabolomics approach. Results: The results demonstrate that metabolomics had the ability to trace the geographical origins of GF. We found that antioxidant activities varied with different varieties of GF, which was dependent on their chemical compositions. The key chemical categories were obtained as the primary contributors of the antioxidant activity, including prenol lipids, flavonoids, coumarins and derivatives, as well as steroids and steroid derivatives. In addition, adouetine Y, coagulin R 3-glucoside and epicatechin 3-glucoside were identified as potential biomarkers for the antioxidant activity of GF. Conclusions: Therefore, our study sheds light on the metabolic characteristics and biomarkers of the antioxidant properties of GF, contributing to the selection and cultivation of a high antioxidant variety. [ABSTRACT FROM AUTHOR]

AbstractNovel trans-2,3-dihydrofuro[3,2-c]coumarins were synthesized and assessed for their inhibition potential against cysteine proteases: cathepsin B, H and L which are the possible targets for anticancer activity. In general, the coumarin derivatives were found to be exceptional inhibitors against this class of enzymes. On the basis of molecular modeling data and structure–activity relationships, their inhibition patterns are also discussed. The selectivity of designed compounds as inhibitors against cathepsins B, H and L was demonstrated by enzyme inhibition data. Enzyme kinetics investigations were also on par with in vitro studies when tested on HepG2 carcinoma cell line utilizing 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. Possible protein–drug interactions responsible for potential inhibition are demonstrated using docking studies. [ABSTRACT FROM AUTHOR]

Coumarins are the backbone of numerous drugs for rare diseases, and the efficient multiphase catalytic synthesis of coumarins remains a great challenge. In this article, a dicarboxyl porous organic polymer coordinated palladium catalyst, Pd-PV-MS, was synthesized by a free radical copolymerization method. The catalyst was characterized and used in the electrophilic addition reaction of phenols and alkynoates for the synthesis of coumarin derivatives. The results demonstrated that, in most cases, high product yields could be obtained with only a small amount of the catalyst (below 2.4 mol %). The catalyst can be applied to a broad range of substrates with high catalytic performance. Moreover, the catalyst can be reused several times without loss of catalytic activity. [ABSTRACT FROM AUTHOR]

An efficient method was developed for the synthesis of eight novel functionalized 1,2,4,3-triazaphospholes and one 1,3,2-thiazaphosphinine incorporating a coumarin ring. Additionally, two interesting examples of diethyl coumarinyl phosphonate and diethyl chromeno-[3,4-c][1,2,4]triazolo[4,3-a]pyridinyl phosphonate were obtained. The proposed methodology involved the treatment of N'-benzoyl-2-oxo-2H-chromene-3-carbohydrazonamide (2) with various phosphorus agents, including phosphorus halides, phosphorus triamide, phosphorus esters, and phosphorus sulfides. IR, NMR, and mass spectrometric methods were used to confirm the structures of the prepared compounds. The antiproliferative properties of the isolated compounds were screened against HepG-2, MCF-7, and A549 cancer cells. The products 5, 7, 9, and 10 exhibited excellent cytotoxic properties compared with doxorubicin. These four bioactive compounds have low toxicity in healthy human HFB4 cells. [ABSTRACT FROM AUTHOR]

A series of novel coumarin derivatives was successfully synthesized by combining the coumarin skeleton with a benzylamine moiety. These derivatives showed better antibacterial activities in vitro tests, especially compound, which was particularly effective. The mechanism of the antibacterial action of compound was thoroughly investigated, and the experimental results revealed that compound was able to increase the permeability of bacterial cell membranes, leading to the disruption of Xoc membranes and effectively inhibiting bacterial growth and reproduction. This finding not only elucidates the antibacterial mechanism of compound, but also provides an important scientific basis for the development of new antibacterial agents in the future. [ABSTRACT FROM AUTHOR]

Novel coumarin derivatives were synthesised and tested for their cytotoxicity against human cancer cells (PC-3 and MDA-MB-231). Compounds 5, 4b, and 4a possessed potent cytotoxic activity against PC-3 cells with IC50 3.56, 8.99, and 10.22 µM, respectively. Compound 4c displayed cytotoxicity more than erlotinib in the MDA-MB-231 cells with IC50 8.5 µM. Moreover, compound 5 exhibited potent inhibitory activity on EFGR with IC50 0.1812 µM, as well as PI3Kβ inhibitory activity that was twofold higher than LY294002, suggesting that this compound has a dual EGFR and PI3Kβ inhibiting activity. Docking aligns with the in vitro results and sheds light on the molecular mechanisms underlying dual targeting. Furthermore, compound 5 decreased AKT and m-TOR expression in PC-3 cells, showing that it specifically targets these cells via the EGFR/PI3K/Akt/m-TOR signalling pathway. Simultaneously, compound 5 caused cell cycle arrest at S phase and induced activation of both intrinsic and extrinsic apoptotic pathways. [ABSTRACT FROM AUTHOR]

Due to the unique color-changing properties of polydiacetylene (PDA), it has been extensively investigated for designing various types of chemo-sensors for the detection of different target analytes. In this article, we have explored the thermodynamic and structural characteristics of Langmuir monolayers formed by 10,12-heptacosadiynoic acid (HCDA), coumarin derivatives (MOCO), and their mixtures to tune PDA phases for demonstrating suitable sensing applications. Analysis of pressure-area (π − A) isotherms, excess area, and Gibbs free energy reveals that pure HCDA and its mixtures with MOCO exhibit significant variations in monolayer behavior, particularly in trilayer formation, which is crucial for polymerization. The results show that all the mixed monolayers display non-ideal mixing behavior, with positive excess area and Gibbs free energy indicating repulsive interactions. Whereas, at a 0.9 mole fraction of HCDA, the repulsion is less and mixing is closer to ideal behaviour. Compression modulus (Cs−1) analysis further explores the phase transitions of the PDA monolayers. Brewster Angle Microscopy (BAM) images provide visual confirmation of structural changes and polymerization under UV illumination. Spectroscopic characterization reveals that phase transitions from blue to red significantly influenced by the presence of MOCO. Additionally, the HCDA/MOCO mixed monolayers of 0.9 mole fraction of HCDA demonstrate enhanced sensitivity to volatile organic compounds (VOCs). This research demonstrates the potential of HCDA and its mixtures with MOCO in developing advanced PDA-based sensors for VOC detection. [ABSTRACT FROM AUTHOR]

Multi-target-directed ligands (MTDLs) represent a promising frontier in tackling the complexity of multifactorial pathologies like Alzheimer's disease (AD). The synergistic inhibition of MAO-B, MAO-A, and AChE is believed to enhance treatment efficacy. A novel coumarin-based molecule substituted with O-phenylpiperazine via three- and four-carbon linkers at the 5- and 7-positions, has been identified as an effective MTDL against AD. Employing a medicinal chemistry approach, combined with molecular docking, molecular dynamic simulation, and ΔGbind estimation, two series of derivatives emerged as potent MTDLs: 8-acetyl-7-hydroxy-4-methylcoumarin (IC50: 1.52–4.95 μM for hAChE, 6.97–7.65 μM for hMAO-A) and 4,7-dimethyl-5-hydroxycoumarin (IC50: 1.88–4.76 μM for hMAO-B). They displayed binding free energy (ΔGbind) of −76.32 kcal/mol (11) and −70.12 kcal/mol (12) against AChE and −66.27 kcal/mol (11) and −62.89 kcal/mol (12) against MAO-A. It is noteworthy that compounds 11 and 12 demonstrated efficient binding to both AChE and MAO-A, while compounds 3 and 10 significantly reduced MAO-B and AChE aggregation in vitro. These findings provide structural templates for the development of dual MAO and AChE inhibitors for the treatment of neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Polycyclic aromatic compounds encompass a diverse array of molecules that exhibit remarkable chemical activity and play pivotal roles across various scientific domains. Coumarins represent a diverse class of heterocyclic compounds, which exhibit a wide range of significant biological and pharmacological activities, while containing at least two aromatic rings in their structure. Because chemical, biological, as well as pharmacological properties and activities are highly dependent on the structural characteristics of the molecule, in this paper a detailed structural investigation of the monocrystal structure of newly synthesized (E)-N′-(1-(2,4-dioxochroman-3-ylidene)ethyl)-3,4,5-trimethoxybenzohydrazide was performed. The DFT model that is best suited for describing the structural parameters of coumarin-benzohydrazides was determined. Out of three tested models which were previously proven to be excellent in describing structures of organic compounds, B3LYP-D3BJ was found to be the best in describing the structure of investigated coumarin derivative in regard to the obtained X-ray and spectroscopic data. Determination of the best theoretical model allows for better structural characterization of the coumarin-benzohydrazides for which monocrystals and consequently X-ray structure cannot be obtained. Finally, both experimental and computational analysis indicated (with high mutual correlation) that investigated compound showed excellent binding potential toward the albumin, indicating good distribution through the organism. [ABSTRACT FROM AUTHOR]

The major threat to public health due to the outbreak of severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) infection has been recognised as a global issue. The increase in morbidity is primarily due to the lack of SARS‐CoV‐2 specific drugs. One of the major strategies to combat this threat is to deactivate the enzymes responsible for the replication of corona virus. To this end, 3‐arylidene/3‐hydroxycoumarin induced deactivation of 3‐chymotrypsin like protease (3CLpro) enzyme, which takes the pivotal role in the replication and maturation, was investigated. For ready availability of the compounds for the above investigation, we have developed a user‐friendly protocol for the synthesis 3‐hydroxycoumarin derivatives from cheap and readily available starting materials in two steps; i) Bronsted acid catalysed Friedel‐Crafts alkylation of phenols with Morita‐Baylis‐Hillman adducts followed by intramolecular lactonization to trans‐3‐arylidenechroman‐2‐ones in one‐pot and ii) ozonolysis in reasonably good yields. Pharmacokinetic assessments of coumarin derivatives revealed drug‐like characteristics with moderate or low toxicity values. Notably, these hydroxycoumarins exhibited enhanced binding affinity against the 3CL protease of SARS‐CoV‐2, fitting well into the binding pocket akin to the previously studied inhibitor N3. Furthermore, a molecular dynamics study elucidated the dynamic behaviour of these small molecules when bound to the protein, showcasing intriguing complexities within the active site. Despite backbone variations and residual fluctuations, compounds 3 d–f and 6 a exhibited a consistent behaviour, instilling confidence in the therapeutic potential of these coumarins for combating SARS‐CoV‐2. [ABSTRACT FROM AUTHOR]

Multi‐component doping has become an effective way to achieve efficient room‐temperature phosphorescence. In this paper, green phosphorescence emission from coumarin derivatives, i.e., coumarin‐3‐carboxylic acid (CCA) and coumarin‐3‐carboxylic ester (CEt) are activated by doping them into polyvinyl alcohol (PVA) matrix (two component doping). Then, a series of metal salts (Ca2+, Al3+, Mn2+, and Zn2+) are added as the third component to construct three‐component doping system, with the aim to further improve the phosphorescence properties of the polymer films. Among them, CaCl2 can significantly increase the emission intensity (9.2 times), prolong the phosphorescence lifetime (up to 361 ms), and increase the phosphorescence quantum yield (from 1.02% to 9.19%). The results indicated that RTP emission can be activated by inhibiting the non‐radiative transition of coumarin derivatives embedded in the rigid PVA matrix. RTP performance can be further enhanced relying on the coordination effect between the coumarin guests and the metal salts. This study provides a simple and effective three‐component doping method for boosting polymer film‐based phosphorescence performance. [ABSTRACT FROM AUTHOR]

AbstractPancreatic ductal adenocarcinoma (PDAC) is one of the deadliest diseases. Here are investigated two synthesized and two hypothetical coumarin derivatives, and their capacity to be used in the PDAC targeted treatment. The inhibitory activity of these four molecules against PARP, ATM, and CHK1 proteins responsible for DNA molecule repair was examined by docking and molecular dynamic analysis. ADMET analysis was applied to determine the pharmacokinetic properties of the tested compounds. The applied theoretical approach showed that the biomedical activity of the investigated coumarins is comparable to the inhibitory activity and pharmacokinetic properties of Olaparib, already used in the PDAC treatment. [ABSTRACT FROM AUTHOR]

Background: The aim of this research is the synthesis and characterization of coumarin-palladium complex and the investigation of the cytotoxicity of both the ligand and the complex. Methods: The palladium(II) complex (CC) was obtained in the reaction between (E)-3-(1-((4-hydroxy-3-methoxyphenyl)amino)ethylidene)-2,4-dioxochroman-7-yl-acetate (CL) and potassium-tetrachloropalladate(II) and characterized using IR and NMR spectra, experimentally and theoretically. Cytotoxicity of CL and CC were determined for human cervical carcinoma HeLa, ovarian cancer A2780, hormone dependent breast cancer MCF7, and colorectal cancer HCT116 lines. The interaction of investigated compounds with HSA was followed by spectrofluorimetric method. The binding mechanism in the active pocket was assessed via molecular docking simulations. Results: A low mean absolute error between experimental and theoretical data proved that the optimized structure corresponded to the experimental one. Both compounds showed a satisfactory selectivity index towards neoplastic cells. The binding affinity of tested compounds to the HSA were confirmed. The molecular docking showed a much lower change in the Gibbs free energy of binding for CC compared to CL. Conclusions: The obtained results revealed that CL and CC exhibit significant effects on several cancer cell lines and good binding properties to HSA, while molecular docking discovered that CC has the most pronounced activity against alpha-fetoprotein. [ABSTRACT FROM AUTHOR]

Blue light (BL) mediated photodynamic therapy (PDT) can not only effectively kill drug-resistant bacteria, but also reduce the damage to deep tissues, providing a new opportunity for the treatment of drugresistant bacterial infections. However, the blue light photosensitizers used in PDT against bacteria are very limited, and it is urgent to develop new blue light photosensitizers to overcome the growing problem of drug resistance of bacteria. Coumarin derivatives exhibit many biological activities, such as anti-inflammatory, antibiosis and anti-tumor, as well as good photosensitivity and stability. Herein, the bactericidal effects of coumarin derivative CDOCA-mediated PDT against methicillin-resistant Staphylococcus aureus (MRSA) were studied. The results showed that 32 μg/mL CDOCA irradiated with blue light (445 nm, 0. 5 W/cm²) for 5 min could completely inhibit the vitality of planktic bacteria. Moreover, CDOCA (48 μg/mL) combined with blue light (0. 5 W/cm², 6 min) could fully eliminate MRSA wrapped in biofilm and degrade biofilm. More importantly, the combined treatment of CDOCA (1 mg/kg) and BL (0. 5 W/cm², 6 min) for 8 days effectively eradicated the biofilm on the skin wounds of mice, reduced inflammation and promoted wound healing. CDOCA-mediated PDT provided in this study is expected to be used in the treatments of drug-resistant bacterial infections. [ABSTRACT FROM AUTHOR]

A benzene ring and a lactone ring combine to form the chemical coumarin. Dye lasers have made significant advances in laser technology. The coumarin molecule itself is a non-fluorescent but it displays high fluorescence when electron-denoting substituents such as sulfonamide, benzopyrone, amine, benzothiazole, hydroxyl, methoxy are substituted at various positions. Substituted coumarin possesses the highest energy properties, photostability, and alteration in electron mobility, and therefore could be effectively used as dye lasers. These are considered some of the best fluorophores due to their outstanding photophysical and photochemical properties, which include high fluorescence quantum yields, great photostability, good functionality, and a wide spectrum range. Various inorganic materials are used in classic laser technology to generate the necessary emission. Inorganic lasers come in various types and can emit light in the electromagnetic spectrum's ultraviolet, visible, or infrared parts. Inorganic lasers have certain limitations, which is why coumarin lasers are becoming increasingly popular due to their many advantages. Compared to inorganic lasers, dye lasers offer far better tunability and cover the entire visible and near-infrared range. They only emit at very few specific wavelengths and in extremely narrow bands. The property is therefore presented in this review. [ABSTRACT FROM AUTHOR]

AbstractCasein kinase 2 (CK2) is an ubiquitous, essential, and highly pleiotropic protein kinase whose abnormally high constitutive activity is suspected to underlie its pathogenic potential in neoplasia and other diseases. Recently, there has been a notable increase in interest in the use of casein kinase 2 (CK2) inhibitors to improve the treatment of a specific form of cancer while minimizing the risk of undesirable side effects. Recently, using different virtual screening approaches, we have identified several novel CK2 inhibitors. In particular, we have discovered that the coumarin moiety can be considered an attractive CK2 inhibitor scaffold. In the present work, quantitative structure-activity relationship (QSAR) analysis has been employed to envisage the inhibitory effects of 32 coumarin derivatives on the CK2 protein. The most efficient model is found by using multiple linear regression (MLR). Its capability is considered by the external and internal validation values found (R2 = 0.884, Q2cv = 0.822, R2pred = 0.821, and R2p = 0.811), which aligned well with Tropsha and Golbraikh’s approach. The highest docking score founded for the newly designed coumarins is −7.50 kcal mol-1, which indicates that candidates can bind to the CK2 receptor with greater affinity. Based on the results of the ADMET properties and drug similarity analyses, a DFT investigation was conducted to confirm the stability of the newly explored compounds. It appears that the most stable complexes are those of compound with the highest binding affinity with a lower risk of toxicité. [ABSTRACT FROM AUTHOR]

Pentacyclic pyrrolocoumarin scaffolds are unique structural motifs that form the backbone of many bioactive compounds. Herein, we report the first-time synthesis of imidazole-fused pentacyclic pyrrolo[3,4-c]coumarin derivatives (2) through the stoichiometric reaction between coumarin-substituted N-heterocyclic carbene (NHC) precursors (1) and Pd(OAc)2, in the presence of an external base. Control experiments revealed that the base-promoted rearrangement of the NHC precursors yields N-(alkyl)aniline-substituted pyrrolo[3,4-c]coumarin derivatives (3), wherein the imidazole ring is opened. Additionally, the formation of 2via the reaction of 3 and Pd(OAc)2 indicated that the formation of pentacyclic pyrrolo[3,4-c]coumarin occurs via the base-promoted rearrangement product of NHC precursors. [ABSTRACT FROM AUTHOR]

Nine new coumarin derivatives of 2‐(7‐hydroxy‐2‐oxo‐2H‐chromen‐4‐yl)acetic acid 6a–i have been successfully synthesized through amide coupling with various substituted anilines and 2‐aminopyridines. The synthesized derivatives were screened for anticancer activity using MTT assay on MCF‐7 cell line. The results showed that compound 6b inhibited MCF‐7 cell growth in a dose‐dependent manner and reached 47% inhibition at 40 µM, being better than starting material 5 and references 3 and 5FU drug. Moreover, 6b inhibited significantly 3D tumorsphere formation. The para‐Br substitution of 6b seems to be important for activity. Docking study suggests estrogen receptor and/or 3a‐HSD type 3 protein could be the target(s) for anticancer activity of this class of compounds. Further optimization of compound 6b should lead to more potent compound. [ABSTRACT FROM AUTHOR]

Herein, we report the fabrication of biomass rice husk‐derived chemically activated carbon (RCAC) sheets which are self‐assembled to 2D hollow porous materials and demonstrated their catalytic efficiency in the domino Knoevenagel−Michael addition reaction for the synthesis of various bio‐active coumarin derivatives in excellent yields under metal‐free conditions mild reaction conditions. Particularly, we have illustrated a facile, eco‐friendly, economical, and sustainable method for the synthesis of bis‐(4‐hydroxycoumarin)methanes, bis‐dimedones, and 4‐hydroxy‐3‐thiomethylcoumarins, via three‐component reactions of 4‐hydroxy coumarin/demedone, aldehydes and or thiophenols. Moreover, the Michael addition of 4‐hydroxy coumarin and chalcone derivatives leading to the synthesis of warfarin derivatives has also been demonstrated using RCAC as a catalyst. The cytotoxicity potential has been performed against human liver cancer cell line Hep‐G2 cancer cells for all the synthesized products by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) method. The cytotoxicity study against Hep‐G2 results indicates that all compounds are capable of killing the liver cancer cell line. The most potent anti‐proliferative activity was observed in compounds 3 g, 5 b, 5 c, 5 a, and 9 b against liver cancer cells. [ABSTRACT FROM AUTHOR]

Current treatments for gynecological cancers include surgery, radiotherapy, and chemotherapy. However, these treatments often have significant side effects. Phytochemicals, natural compounds derived from plants, offer promising anticancer properties. Coumarins, a class of benzopyrone compounds found in various plants like tonka beans, exhibit notable antitumor effects. These compounds induce cell apoptosis, target PI3K/Akt/mTOR signaling pathways, inhibit carbonic anhydrase, and disrupt microtubules. Additionally, they inhibit tumor multidrug resistance and angiogenesis and regulate reactive oxygen species. Specific coumarin derivatives, such as auraptene, praeruptorin, osthole, and scopoletin, show anti-invasive, anti-migratory, and antiproliferative activities by arresting the cell cycle and inducing apoptosis. They also inhibit metalloproteinases-2 and -9, reducing tumor cell migration, invasion, and metastasis. These compounds can sensitize tumor cells to radiotherapy and chemotherapy. Synthetic coumarin derivatives also demonstrate potent antitumor and anticancer activities with minimal side effects. Given their diverse mechanisms of action and minimal side effects, coumarin-class phytochemicals hold significant potential as therapeutic agents in gynecological cancers, potentially improving treatment outcomes and reducing side effects. This review will aid in the synthesis and development of novel coumarin-based drugs for these cancers. [ABSTRACT FROM AUTHOR]

Coumarins are the natural products which are characterized as 1,2-benzopyrones. The discovery of coumarins is done with enlarged chemical space through many synthetic course of action. They are found in many plants such as cinnamon, tonka beans, and sweet clover. Cassia cinnamon has the highest amount of coumarin whereas Ceylon cinnamon has the lowest. Many biological activities and applications of coumarins are attributed to their capacity to engage in non-covalent interactions with numerous enzymes and receptors found in living organisms. Some of the pharmacological properties are anticancer, anticoagulant, antifungal, antiviral, antitubercular, antioxidant, anti-inflammatory, antidiabetic, antibacteria, antihypertensive, antihyperglycemic, anticonvulsant, antiparasitic, antineurodegenerative, etc. A review has been carried out based on various pharmacological activities containing Coumarin derivatives to rationalize the activities based on the structural variations. Coumarin derivatives have been attracting increasing interest for their usefulness and excellent contribution in the prevention, curing, and treatment of the diseases, growth modulation, cell growth and regulation of immune response. [ABSTRACT FROM AUTHOR]

Objective: This work reported for the first time the synthesis of novel hybrids described as a five-membered ring with three heteroatoms fused on the 6,7-coumarin framework. This is an endeavor to discover adaptable and easily obtainable coumarin frameworks possessing a wide array of biomedical characteristics. Methods: Seven hybrids constructed from 1,3,2-dioxathiole-2-oxide and coumarin derivatives were fabricated through a three-step synthetic process originating from benzene 1,2,4-triole. Spectroscopic methodologies, encompassing 1H, 13C NMR, and FT-IR, were utilized to validate the structural framework of the synthesized hybrids. Their potential in the biomedical realm to function as antitumor agents, suppressors of inflammation, oxidative stress alleviators, and regulators of blood sugar levels was assessed. In addition, their cytosafety and in silico pharmacokinetic parameters were also investigated. Six cancerous cell lines were utilized to investigate the antitumor activity of the synthesized hybrids through the MTT-dependent assay, while three noncancerous cell lines were employed to examine the compounds' cytocsafety. The inflammatory suppressant potential was investigated against three inflammatory-related enzymes. The antioxidant activity was investigated in oxidative stress-induced human cells, while the antidiabetic potential was investigated through two carbohydrate-digesting enzymes. Finally, two web-based programs were utilized to reveal the pharmacokinetic profiles of the title hybrids. Results and Discussion: Four principal outcomes were reported based on the extracted findings. The dioxathiole-coumarin hybrids have encouraging and extensive biomedical impacts. Hybrid (DOT3) had potent antitumor, antioxidant, and cytosafety potentials. Compound (Precursor O-III) exhibited potent anti-inflammatory potential through the lipoxygenase-dependent pathway (IC50 = 9.22 ± 1.02 µg/mL). Compounds (DOT1) and (DOT2) have significant potential as antidiabetic agents, as evidenced by their potent inhibition capacities toward glucosidase and amylase. Conclusions: Compounds (DOT3), (Precursor O-III), (DOT1), and (DOT2) exhibited the potential to function as valuable scaffolds for screening novel medications with antitumor, antioxidant, anti-inflammatory, and antidiabetic properties in the foreseeable future. [ABSTRACT FROM AUTHOR]

DNA nanostructures have been regarded as promising platforms for molecular information coding for their high programmability and nanoscale addressability. However, steganography based on DNA nanostructures still needs further investigation. Here, we designed and synthesized a coumarin derivative structure with selective photo responsiveness in the visible light spectrum and developed a DNA origami steganography system that can only be decrypted through specific light exposure conditions. Under right light treatment, the effective cleavage of photoresponsive groups would cause some of the streptavidin binding sites to detach from the origami, thereby allowing the steganographic information to be read correctly. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus infections are the primary causes of morbidity, and mortality, particularly in immuno-compromised individuals. S. aureus associated infections are acquired from community, as well as hospital settings, and difficult to treat because of the emerging resistance against available antibiotics. One of the key factors of its resistance is the biofilm formation, which can be targeted to treat S. aureus-induced infections. Currently, there is no drug available that function by targeting the biofilm. This unmet need demands the discovery of drug candidates against S. aureus biofilm. The present study was designed to evaluate coumarin derivatives 1–21 against S. aureus biofilm. The 96-well plate crystal violet assay was employed for the quantification of biofilm. Results showed that the coumarin derivatives 2–4, 10, and 17 possess potent antibiofilm activity, with MBIC values between 25–100 μg/mL. The results were further confirmed through atomic force microscopy (AFM), scanning electron (SEM), and fluorescence microscopic studies. The quantitative RT-PCR analysis revealed the downregulation of biofilm associated genes, icaA and icaD. These coumarin derivatives were also found to be non-cytotoxic to fibroblasts. This study, therefore, identifies the antibiofilm potential of coumarin derivatives that will pave the way for further research on these derivatives. [ABSTRACT FROM AUTHOR]

Thymus atlanticus is an aromatic and medicinal plant endemic to Morocco characterized by important morphological polymorphism. The objective of this study is to determine the chemical polymorphism of T. atlanticus collected in different regions of Morocco. The analysis of essential oils (EOs) was carried out by gas chromatography-mass spectrometry (GC-MS). In total, 88 components were identified, among them, eleven compounds are major: o-Cymene, α-terpinene, thymol methyl ether, geraniol, thymol, p-cymen-7-ol, carvacrol, nerolidol, shyobunol, a-terpinyl acetate, and linalool. We determined eight chemotypes: Thymol (2.0%) and thymol methyl ether (19.0%) chemotype, carvacrol (31.7%) and thymol (22.4%) chemotype, geraniol (33.8%) and carvacrol (23.3%) chemotype. The sites, Oukaimeden, Tizi n'Tichka and Tizi n'Ait Imi characterized by a single majority compound for each; nerolidol (37.0%) at Oukaimeden, carvacrol (28.7%) for Tizi n'Tichka and shyobunol (26.3%) for Tizi n'Ait Imi. However, Saghro EO characterized by several major compounds; α-terpinene (19.4%), p-cymene-7-ol (16.0%), o-cymene (15.9%), thymol (13.1). On the other hand, Tizi n'Talghemt characterized by several major compounds; linalool (28.2%), a-terpinyl acetate (28.7). Asteraceae, Rutaceae, and Fabaceae. The health-promoting properties of coumarins and their derivatives were found to be extensive. Many studies have reported their antioxidant, anti-inflammatory, anticancer, antibacterial, and antifungal activities. The compounds have shown potential in protecting against cardiovascular diseases, neurodegenerative disorders, diabetes, and obesity. Understanding the structure-activity relationships of these compounds is crucial for further research and development in this area. [ABSTRACT FROM AUTHOR]

Coumarins and their derivatives are bioactive compounds recognized for their diverse range of health-promoting properties. This systematic review aims to identify and summarize the natural sources of coumarins and their derivatives. Electronic databases, including PubMed, Scopus, and Web of Science, were thoroughly searched with precise keywords and inclusion/exclusion criteria. Studies published in English from 2000 to 2023 were considered for inclusion. Natural sources of coumarins and their derivatives were identified, including plants, fungi, and bacteria. Some common plant families known to contain coumarins and their derivatives were Asteraceae, Rutaceae, and Fabaceae. The health-promoting properties of coumarins and their derivatives were found to be extensive. Many studies have reported their antioxidant, antiinflammatory, anticancer, antibacterial, and antifungal activities. The compounds have shown potential in protecting against cardiovascular diseases, neurodegenerative disorders, diabetes, and obesity. Understanding the structure-activity relationships of these compounds is crucial for further research and development in this area. [ABSTRACT FROM AUTHOR]

Halogen bonds find application in supramolecular chemistry, DNA Holliday junction, drug design, organic catalysis and various other fields. Coumarin derivatives are high in demand due to their application in photochemotherapy, drugs and other cancer treatments. Halogenated coumarins are widely known for their biological activities. There exists a competition between the halogen bond and hydrogen bond in singly hydrated halogenated coumarins. The competition between hydrogen and halogen bonding interactions in 3-halogenated 4-hydroxyl coumarin [coumarin derivative; halogen, X = F (A), Cl (B), Br (C), I (D)] with water molecule in the corresponding binding regions C3–X and C2=O4 is studied. This study was conducted using PBE0 D3BJ with augmented correlation consistent basis set in order to include the diffuse functions. Improved findings for non-bonded distances and much more distinct intramolecular effects were obtained using BJ-damping. In the singly-hydrated systems, the water molecule forms a hydrogen bond with C2=O4 in all the halogenated molecules, whereas halogen bonding between the water oxygen and C2–X exists only in the case of X = Br (C) and I (D). The absence of a halogen-bonded structure in singly-hydrated chlorine and fluorine substituted coumarin derivative is therefore attributed to the competing hydrogen-bonding interaction with C2=O4. RDG scatter plot as well QTAIM analysis implied that halogen bond exists between water molecule and the coumarin derivative. Further, the most modern local energy decomposition (LED) analysis of intermolecular interaction was also studied using DLPNO-CCSD(T). Finally, ab initio molecular dynamics was also performed. [ABSTRACT FROM AUTHOR]

In the present article, the inhibitory activity against the postharvest fungi Lasiodiplodia spp., Botrytis spp., and Fusarium spp. of coumarin was evaluated. Coumarin exhibited a significant antifungal effect (at concentrations of 1.5 mM and above), with inhibition percentages ranging from 24.8% to 66.4% for Lasiodiplodia spp., 55.5% to 78.8% for Fusarium spp., and 75.6% to 88.9% for Botrytis spp. Additionally, the metabolism of coumarin by phytopathogenic fungi was studied. Coumarin was found to be transformed into two main metabolic products, which were purified by chromatographic techniques and identified by spectroscopic methods (¹H and 13C NMR), corresponding to dihydrocoumarin and 3-(2-hydroxyphenyl) propanoic acid. According to the structure of metabolic products, coumarin was hydrogenated at the carboncarbon double bond and the lactone system was opened, which affects the α,β-unsaturated carbonyl system. Additionally, the effect of different substituents on both the aromatic ring and the α, β-unsaturated carbonyl system in the antifungal activity was evaluated. The results indicate that the presence of substituents such as 3-acetyl and 3-ethyl carboxylate on the double bond moiety significantly enhances the inhibitory effect on the radial growth of postharvest pathogen Lasiodiplodia spp. [ABSTRACT FROM AUTHOR]

Coumarin and its derivatives, presenting in many organisms (plants, fungi, and bacteria), are critical metabolites composed of fused benzene and α-pyrone rings. With unique biological and chemical properties, coumarin derivatives possess great technological potential in the agrochemicals, pharmaceuticals, food, and cosmetic industries. The increasing demand for coumarin derivatives accelerates the research in biological and chemical synthesis to provide stable and scalable sources of coumarins. However, the complex structures and unknown pathways have limited the progress in the biosynthesis of coumarin derivatives. Here, we summarize recent developments and provide a detailed analysis of coumarin derivative biosynthetic pathways in different organisms.

In this study, we investigated the antibacterial activity of the coumarin component isolated from lime peel and coumarin derivatives synthesized using various techniques against eight types of food-poisoning bacteria. The minimum inhibitory concentration (MIC) for the 3b [5,7-dihydroxy-4-trifluoromethylcoumarin] derivative was measured as 1.5 mM in Bacillus cereus, Micrococcus luteus, Listeria monocytogenes, and Staphylococcus aureus subsp. aureus; that for the 3c [7-hydroxy-4-trifluoromethylcoumarin] derivative was 1.7 mM in Enterococcus facium; and that for the 3n [dicoumarol] derivative was 1.2 mM in L. monocytogenes. These results confirmed that coumarin derivatives with CF3 and OH substituents had enhanced antibacterial activity. [ABSTRACT FROM AUTHOR]

Context: Corrosion, the degradation of materials due to chemical reactions with their environment presents significant challenges both economically and environmentally. It affects various industries, including construction, transportation, and manufacturing, leading to equipment failures, safety hazards, and increased maintenance costs. Coumarin derivatives have shown promise due to their inherent chemical properties and potential for biodegradability. In this study, a series of the coumarin derivatives were examined in silico to reveal their potential corrosion inhibition properties toward the Fe(110) and Cu(111) surfaces. The compounds investigated include coumarin (2H-chromen-2-one, 1), furanocoumarin (7H-furo[3,2-g]chromen-7-one, 2), dihydrofurano coumarin (2,3-dihydro-7H-furo[3,2-g]chromen-7-one, 3), pyrano coumarin–linear type (8,8-dimethyl-2H,8H-pyrano[3,2-g]chromen-2-one, 4), pyrano coumarin–angular type (8,8-dimethyl-2H,8H-pyrano[2,3-f]chromen-2-one, 5), bicoumarin (3,3'-methylenebis(2H-chromen-2-one), 6), and phenyl coumarin (4-phenyl-2H-chromen-2-one, 7). The findings suggest that the bicoumarin derivative 6 exhibits the lowest adsorption energy with the Fe(110) surface, while the same energy absolute value is about two times lower for the Cu(111) surface. This is due to the formation of a planar configuration of a molecule of 6 on the metal surfaces with the participation of both coumarin fragments upon interacting with the Fe(110) surface, while one coumarin fragment interacts with the Cu(111) surface. Methods: Density functional theory (DFT) calculations were employed to study the electronic properties of the coumarin derivatives. The specific computational method used was B3LYP, a hybrid functional that combines with the 6–311 + + G(d,p) basis set. Each coumarin derivative was first subjected to a geometry optimization to find the most stable molecular structure. Electronic properties, dipole moments, and molecular electrostatic potential surfaces were calculated. The Monte Carlo simulations were used to model the adsorption behavior of the coumarin derivatives on metal surfaces, namely, Fe(110) and Cu(111). These simulations allowed to visualize interaction of the studied molecules with the metal surfaces, which is crucial for their function as corrosion inhibitors. The present study provides a comprehensive understanding of the corrosion inhibition potential of the applied coumarin derivatives. The insights gained from these methods can inform the development of effective, sustainable corrosion inhibitors that are both environmentally friendly and highly efficient. [ABSTRACT FROM AUTHOR]

Molecular dynamics (MD) simulation is an in silico method used in the biomolecular level of research to study how the protein interacts with the target with time. It provides a detailed information of the protein dynamics and ligand structure with the crucial amino acid interactions. Monoamine oxidase B (MAO−B) is a crucial isoenzyme responsible for the catalyses of oxidative deamination of various biogenic amines in the brain and peripheral tissues. The selective inhibitors of MAO−B are considered as the management of symptoms of neurodegenerative disorders like Alzheimer's disease(AD) and Parkinson disease(PD). Recently the structural scaffolds containing chalcones, coumarins and chromones derived candidates shown potent, selective, competitive and reversible type of MAO−B inhibitors. The structural similarities between the above scaffolds can produce almost similar type of interactions in the inhibitor binding cavity of MAO−B. Numerous molecular simulation reports were supported by the above mentioned fact. The current review focus on the last ten year molecular dynamics report of chalcones, coumarins and chromones towards MAO−B inhibition. The review also focuses on the software details used in the MD dynamics simulation and the structural requirement from each class of compound for the recognition of MAO−B inhibitory activity. [ABSTRACT FROM AUTHOR]

In this study, a coumarin derivative, 3-Acetyl-2-oxo-2H-chromene-6-carbohydrazide that could be a new antifungal agent was synthesised, and characterised by elemental analysis, FT-IR, 1H and 13C NMR spectroscopic techniques. DFT calculation data (IR, 1H, and 13C NMR chemical shifts) reveals the good correlation with the experimental values to support the structure of the compound. Molecular geometry, stability, reactivity, and spontaneity were also predicted based on frontier molecular orbitals (FMO), electrostatic potential (ESP) and thermodynamic parameters like entropy, enthalpy, and Gibbs free energy. In addition, molecular docking study results implicate its strong binding (−7.1 to −7.8 kcal/mol) and inhibitory activity against four pathogenic fungal strains A. niger (5GHL), P. chrysogenum (3A72), S. cerevisiae (4G4S), and N. crassa (6MVJ). Thus, this compound may be considered biologically important and serve as a lead for the development of antifungal agents. [ABSTRACT FROM AUTHOR]

As an increasingly well-known derivative of coumarin, daphnetin (7,8-dithydroxycoumarin) has demonstrated various pharmacological activities, including anti-inflammation, anti-cancer, anti-autoimmune diseases, antibacterial, organ protection, and neuroprotection properties. Various studies have been conducted to explore the action mechanisms and synthetic methods of daphnetin, given its therapeutic potential in clinical. Despite these initial insights, the precise mechanisms underlying the pharmacological activities of daphnetin remain largely unknown. In order to address this knowledge gap, we explore the molecular effects from the perspectives of signaling pathways, NODlike receptor protein 3 (NLRP3) inflammasome and inflammatory factors; and try to find out how these mechanisms can be utilized to inform new combined therapeutic strategies. [ABSTRACT FROM AUTHOR]

Coumarins, which are 2H-1-benzopiran-2-one compounds originating from some plants, have been proven to be anticancer, antibacterial, and anticancer agents. Around of these structures are currently accepted for the treatment of cardiovascular disease (warfarin), antibiotics (novobiocin or chlorobiocin), and anticancer medications (geiparvarin). We created 38 coumarin derivatives (2-50), 22 of which were novel, in this project by replacing the eighth carbon of the benzopiran ring with nearly aromatic and aliphatically substituted piperidine and piperazines. This was done because of the structure's great potential and the dearth of research on molecules resulting from the benzopiranone heterocycle. The produced compounds' cytotoxicity, analgesic, and anti-inflammatory qualities were evaluated. The targeted molecules were made in two steps. Using the Pechmann reaction, the 7-hydroxy-4-methyl-chromen-2-one coumarin scaffold was created in the first step. Another phase was the derivatization of the 7-hydroxy-4-methyl-chromen-2-one coumarin scaffold (compound 1) by addition of piperidine and aromatic and aliphatic substituted piperazine groups. In vitro tests were used to evaluate the cytotoxicity, analgesic, and anti-inflammatory properties. MTT assay was employed to assess the cytotoxicity of MCF-7 breast cancer cells and RAW264.7 macrophages. The nitrite inhibition test was employed to evaluate anti-inflammatory activity using RAW264.7 macrophage cells. The reference drugs for the cytotoxicity and anti-inflammatory tests were L-NAME and indomethacin (IND). PGE2 production for the painkilling effect was noted. The outcomes indicated that compounds 11, 23, and 31 have promising anti-inflammatory activity. Compound 11 produced better results than the reference drugs and were three times more active than IND. Moreover, compound 11 confirmed little cytotoxicity and a moderate analgesic effect. [ABSTRACT FROM AUTHOR]

Hybridized local and charge‐transfer (HLCT) with the utilization of both singlet and triplet excitons through the "hot excitons" channel have great application potential in highly efficient blue organic light‐emitting diodes (OLEDs). The proportion of charge‐transfer (CT) and locally excited (LE) components in the relevant singlet and triplet states makes a big difference for the high‐lying reverse intersystem crossing process. Herein, three novel donor (D)‐acceptor (A) type HLCT materials, 7‐([1,1′‐biphenyl]‐4‐yl(9,9‐dimethyl‐9H‐fluoren‐2‐yl)amino)‐3‐phenyl‐1H‐isochromen‐1‐one (pPh‐7P), 7‐([1,1′‐biphenyl]‐4‐yl(9,9‐dimethyl‐9H‐fluoren‐2‐yl)amino)‐3‐methyl‐1H‐isochromen‐1‐one (pPh‐7M), and 6‐([1,1′‐biphenyl]‐4‐yl(9,9‐dimethyl‐9H‐fluoren‐2‐yl)amino)‐3‐methyl‐1H‐isochromen‐1‐one (pPh‐6M), were rationally designed and synthesized with diphenylamine derivative as donor and oxygen heterocyclic coumarin moiety as acceptors. The proportions of CT and LE components were fine controlled by changing the connection site of diphenylamine derivative at C6/C7‐position and the substituent at C3‐position of coumarin moiety. The HLCT characteristics of pPh‐7P, pPh‐7M, and pPh‐6M were systematically demonstrated through photophysical properties and density functional theory calculations. The solution‐processed doped OLEDs based on pPh‐6M exhibited deep‐blue electroluminescence with the maximum emission wavelength of 446 nm, maximum luminance of 8755 cd m−2, maximum current efficiency of 5.83 cd A−1, and maximum external quantum efficiency of 6.54 %. The results reveal that pPh‐6M with dominant 1LE and 3CT components has better OLED performance. [ABSTRACT FROM AUTHOR]

Coumarin and aryl hydrazide-hydrazone have attracted our attention due to their vast biological properties. Previous studies suggested that coumarin-tethered aryl hydrazide-hydrazone showed potent activities against HepG2. In the present study, we investigated the cytotoxic potency of the coumarin derivatives 1 - 3 to compare with coumarin hydrazine-hydrazone hybrids 4 and 5 against hepatocellular carcinoma HepG2 and LH86 cell lines. Among the tested coumarins, hybrids 4 and 5 showed highly potent activity against HepG2 with IC50 values of 17.82 ± 2.79 and 7.87 ± 0.88 μg/mL, respectively. The hybrid 4 also showed the strongest activity against LH86 cell line with IC50 values of 48.32 ± 2.64 μg/mL. Further, we have studied the mechanism of action of the hybrid compounds 4 and 5 in HepG2 cells via the flowcytometry analysis and the activation of the caspase-3 and caspase-7. The results showed that hybrids 4 and 5 obviously inhibited the proliferation of HepG2 cell line through inducing apoptosis. [ABSTRACT FROM AUTHOR]

To develop new alkaline phosphatase inhibitors, a series of new azo coumarin derivatives were designed by using computer aided drug designing and virtually assessed using online platforms. At first, the compounds were screened for ADMET, physicochemical properties, drug-likeness, toxicity studies and target prediction using pKCSM, SwissADME, SwissTargetPrediction and ProTox-II tools. The predictions were supported by in silico molecular docking with alkaline phosphatase enzyme using CB-Dock2 molecular docking tool. The compounds possessed good ADMET and physicochemical properties, drug-likeness and devoid of any immunotoxicity and cytotoxicity. The evaluated binding energy values reveal that all compounds fit favorably into the alkaline phosphatase active site displaying hydrogen bonding with different amino acid residues of the target protein and could be good scaffolds for designing new alkaline phosphatase inhibitors. These results collectively framed the way for the development of new azo coumarin derivatives as possible alkaline phosphates inhibitors. [ABSTRACT FROM AUTHOR]

BACKGROUND: Computational research plays an important role in predicting the chemical and physical properties of biologically active compounds important in future structural modifications to improve or modify biological activity. OBJECTIVE: This research focuses on quantum chemical and spectroscopic investigations properties of synthesized 4-hydroxycoumarin derivatives. METHODS: Quantum chemical calculations were obtained using B3LYP, HF, and M06-2x level methods with the 6-31++G (d,p) basis set. Afterward, IR, 1H, 13C, UV-Visible experimentally parameters were compared with the results obtained using the B3LYP/6-31+G*(d) basis set of the molecules to be able to characterize the structures. RESULTS: Based on the quantum chemical calculations compound with acetamido group on the phenyl ring is the most reactive, and compound with nitro substituent is the least reactive and the the strongest electrophile among tested compounds. With the exception of compounds with dimethylamino group, all other compounds have a pronounced tautomer between OH and C = O group. The calculated and experimental values are in agreement with each other. CONCLUSION: The molecular structure in the ground state of six 3-cinnamoyl 4-hydroxycoumarin derivatives was optimized using density functional theory. The observed and computed values were compared and it can be concluded that the theoretical results were in good linear agreement with the experimental data. [ABSTRACT FROM AUTHOR]

Novel miniaturized Pb(II) paper-based potentiometric sensors are described using coumarin derivatives I and II as electroactive ionophores and nano vanadium pentoxide as a solid contact material for the sensitive and selective monitoring of trace lead ions. Density functional theory (DFT) confirms optimum geometries, electronic properties, and charge transfer behaviors of 1:2 Pb(II): coumarin complexes. The sensors are prepared by using two strips of 20 × 5 mm filter paper with two circular orifices. One orifice is coated with vanadium pentoxide (V2O5) nanoparticles in colloidal conductive carbon as a solid-contact, covered by a PVC membrane containing coumarin ionophore to act as a sensing probe. The other orifice is treated with Ag/AgCl in a polyvinyl butyral (PVB) film, to act as a reference electrode. Sensors with ionophores (I) and (II) exhibit Nernstian slopes of 27.7 ± 0.2 and 30.2 ± 0.2 mV/decade over the linear concentration range 4.5 × 10−7 to 6.2 × 10−3 M and 8.5 × 10−8 to 6.2 × 10−3 M, with detection limits of 1.3 × 10−7 M (26.9 ppb) and 2.1 × 10−8 M (4.4 ppb), respectively. The sensors are satisfactorily used for accurate determination of lead ions in drinking water, lead-acid battery wastewater, and electronic waste leachates. The results compare favourably well with data obtained by flameless atomic absorption spectrometry. [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]

The Optical properties of the FBTC (1-((4-((5-chlorobenzo[d]oxazol-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)methyl)-3H-benzo[f]chromen-3-one) molecule were studied experimentally and theoretically. The spectra of absorption and fluorescence were recorded in various solvents to explore their Solvatochromic behavior and dipole moment at room temperature. To determine the ground and excited state of dipole moment experimentally and theoretically, we employed different Solvatochromic techniques, including microscopic solvent polarity functions developed by Lippert, Bakhshiev, Kawaski-Chamma-Viallet, and Reichardt's, as well as density functional theory (DFT) and time-dependent density functional theory (TD-DFT) methods. The stability of the excited state dipole moment in FBTC is higher. Using prime functional, FBTC was optimized in its ground state, and its HOMO (Highest Occupied Molecular Orbital) and LUMO (Lowest Unoccupied Molecular Orbital), energies were estimated. These values were then compared with those obtained through cyclic voltammetry. Based on the HOMO and LUMO values given, we calculated the global reactivity parameter and energy gap, which was found to be low at 3.77 eV. This study also includes an estimation of electron absorption energies and oscillator strength. Natural population analysis (NPA), Milliken atomic charge, and molecular electrostatic potential (MESP) map are correlated. In addition, FBTC exhibited exceptional physiological temperature sensing behaviour from 20 °C -65 °C with high relative sensitivity and firm stability. Hence these results confirm that FBTC is a potential candidate for photonic devices and it's also applicable in optical temperature sensing. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is a chronic metabolic disorder posing a significant health risk. Effective treatments are continually sought. Coumarin derivatives with oxime ester groups have shown potential as antidiabetic agents by inhibiting the α-glucosidase enzyme, a key player in glycoprotein metabolism and postprandial hyperglycemia control. This makes lysosomal α-glucosidase a promising therapeutic target. A study used 28 coumarin derivatives with known α-glucosidase inhibitory IC50 values for computer-assisted drug design (CADD) through quantitative structure-activity relationship (QSAR) analysis, yielding a statistically robust equation for guiding new compound development. Subsequently, eleven new coumarin derivatives with oxime ester groups were synthesized, showing enhanced α-glucosidase inhibitory activity compared to the initial set. Molecular docking assays indicated that compounds 32, 37, 38, and 39 had lower free energy values than the native ligand, suggesting higher stability in target protein interactions. Notably, compound 38 had the lowest free energy (-8.351) and demonstrated lower root mean square deviation (RMSD) and root mean square fluctuation (RMSF) than the original ligand, indicating greater stability. The QSAR equation derived is: Log IC50 = 2.886 - 0.054 (LUMO) + 0.073 (μ) – 0.148 (α) – 0.046 (RD) + 0.046 (BM) + 0.001 (Vvdw) – 0.421 (qC2) + 1.138 (qC8) – 0.092 (qC9) + 2.61 (qC10) + 1.354 (qN1) (Eq 1) n=28; R=0.918; R²=0.843; SD=0.196; F calc/F tab=3.169; Sig =<0.01; PRESS = 1.376. Compound 38’s SMILES notation is: C\C(=N/OC(=O)\C=C/C1=CC=C(Br)C=C1)C1=CC2=CC(O)=C(CC(O)=O)C=C2OC1=O). [ABSTRACT FROM AUTHOR]

Coumarins are a class of naturally occurring compounds found in various plants, fungi, and microorganisms, each with a unique chemical profile. These compounds exhibit a broad range of bioactivities, including antithrombotic, anti-inflammatory, antioxidant, antimicrobial, antiviral, anticancer, and neuroprotective properties. The effective extraction of coumarins, facilitated by methods such as maceration and microwave-assisted extraction, is integral to unlocking their potential across various applications. Nevertheless, safety and toxicology considerations assume paramount importance, particularly in pharmaceuticals, cosmetics, and food additives. While moderate dietary consumption of coumarin-rich foods is generally safe, excessive intake, whether through foods or supplements, raises concerns linked to hepatotoxicity and photosensitivity. Notably, specific coumarin derivatives, including the widely used anticoagulant warfarin, necessitate precise dosing and vigilant monitoring to mitigate the risk of bleeding complications. In conclusion, the versatile biological activities of coumarins underscore their significance; yet, their safety and toxicity profiles are contingent on multiple factors, encompassing compound type, dosage, and individual susceptibility. This review provides a holistic understanding of coumarins, encompassing their natural origins, biosynthesis, bioactivity spectrum, extraction techniques, and insights into safety, and toxicology. [ABSTRACT FROM AUTHOR]