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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]

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]

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]

الملخص: أهداف البحث: هدفت الدراسة إلى إجراء تحليل مقارن لتأثيرات دمج مشتق الكومارين الهيدرازيني في إسمنت أيونومر الزجاج المعدل بالراتنج والتقليدي على معدلات تحررهما وخصائصهما المضادة للبكتيريا. طرق البحث: استخدم إسمنت أيونومر الزجاج المعدل بالراتنج فوجي الثاني وإسمنت أيونومر الزجاج التقليدي عالي الفلورايد فوجي السابع كمجموعات ضابطة. تم تصنيع مشتق الكومارين الهيدرازيني داخليا، ودمجه في كلا النوعين بنسب وزنية واحد وإثنين بالمئة، وتحليله كيميائيا باستخدام مطيافية الأشعة تحت الحمراء. ثم تم تقييم معدلات تحرر مشتق الكومارين الهيدرازيني والفلورايد باستخدام مطياف الأشعة فوق البنفسجية المرئية ومقياس الفلورايد على التوالي. تم تقييم الخصائص المضادة للبكتيريا ضد المكورات العقدية الدموية باستخدام طريقة الانتشار في الآجار وقياس عكارة النمو البكتيري، متبوعا بملاحظة الشكل البكتيري باستخدام المجهر الإلكتروني الماسح. تم تحليل البيانات إحصائيا باستخدام تحليل التباين أحادي الاتجاه واختبار بونفيروني البعدي. النتائج: أكدت أطياف الأشعة تحت الحمراء وجود مشتق الكومارين الهيدرازيني في مصفوفات الإسمنت. تم تحرر المشتق بنجاح من كلا النوعين بكلتا النسبتين الوزنيتين. لوحظ تحرر أعلى للفلورايد ومناطق تثبيط أكبر مقارنة بالمجموعات الضابطة، مع تأثير أكثر أهمية في النوع المعدل بالراتنج. بالإضافة إلى ذلك، أدى دمج المشتق إلى إبطاء نمو المكورات العقدية الدموية وأظهر تغيرات ملحوظة في شكل البكتيريا خاصة في النوع المعدل بالراتنج. الاستنتاجات: أدى دمج مشتق الكومارين الهيدرازيني في كلا نوعي الإسمنت إلى تحسين تحرر الفلورايد وتعزيز الأنشطة المضادة للبكتيريا، مع ملاحظة تأثير أكثر أهمية في النوع المعدل بالراتنج مقارنة بالنوع التقليدي. Abstract: Objective: The study aimed to conduct a comparative analysis of the effects of incorporating hydrazinyl coumarin derivative (HCD) in resin-modified (RMGIC) and conventional glass ionomer cement (cGIC) on their release profiles and antibacterial properties. Method: Resin-modified GIC, Fuji II LC (F2) and high-fluoride cGIC, Fuji VII (F7) were used as controls. HCD was synthesized in-house, incorporated into both RMGIC and cGICs at 1 % and 2 % weight percentages (w/w), and chemically analyzed using Fourier transform infrared (FTIR) spectroscopy. Then, the F2 containing HCD (GIC-HCD F2) and F7 containing HCD (GIC-HCD F7) were evaluated for HCD and fluoride release profiles using UV Visible spectrophotometer and pH/ISE benchtop fluoridemeter, respectively. The antibacterial properties were assessed against Streptococcus sanguinis using the agar well diffusion method and measurement of bacterial growth turbidity, followed by the observation of the bacterial morphology using scanning electron microscope. The data were statistically analyzed using one-way ANOVA and Bonferroni post-hoc tests. Results: The FTIR spectra confirmed the presence of HCD in the GIC-HCD matrices. HCD was successfully released from both GIC-HCD F2 and GIC-HCD F7 matrices at both weight percentages. Higher fluoride release and inhibitory zones were observed compared to the control groups, with GIC-HCD F2 having a more significant effect than GIC-HCD F7. Additionally, the incorporation of HCD slowed down the growth of Streptococcus sanguinis and showed remarkable changes in bacterial shape specifically on GIC-HCD F2. Conclusion: The incorporation of HCD into both RMGIC and cGIC improved fluoride release and enhanced the antibacterial activities, with a more significant effect observed in RMGIC compared to cGIC.

Asymmetric wide‐band gap fullerene‐free acceptors (FFAs) play a crucial role in organic solar cells (OSCs). Here, we designed and synthesized a simple asymmetric coumarin‐anthracene conjugate named CA‐CN with optical band gap of 2.1 eV in a single‐step condensation reaction. Single crystal X‐ray structure analysis confirms various multiple intermolecular non‐covalent interactions. The molecular orbital energy levels of CA‐CN estimated from cyclic voltammetry were found to be suitable for its use as an acceptor for OSCs. Binary OSCs fabricated using CA‐CN as acceptor and PTB7‐Th as the donor achieve a power conversion efficiency (PCE) of 11.13 %. We further demonstrate that the insertion of 20 wt % of CA‐CN as a third component in ternary OSCs with PTB7‐Th : DICTF as the host material achieved an impressive PCE of 14.91 %, an improvement of ~43 % compared to the PTB7‐Th : DICTF binary device (10.38 %). Importantly, the ternary blend enhances the absorption coverage from 400 to 800 nm and improves the morphology of the active layer. The findings highlight the efficacy of an asymmetric design approach for FFAs, which paves the way for developing high‐efficiency OSCs at low cost. [ABSTRACT FROM AUTHOR]

Coumarin, a phenolic compound, is a secondary metabolite produced by plants such as Tanga and Lime. Coumarin derivatives were prepared via Pechmann condensation. In this study, we performed in vitro and in vivo experiments to determine the antimicrobial and gut immune-regulatory functions of coumarin derivatives. For the in vitro antimicrobial activity assay, coumarin derivatives C1 and C2 were selected based on their pathogen-killing activity against various pathogenic microbes. We further demonstrated that the selected coumarin derivatives disrupted bacterial cell membranes. Next, we examined the regulatory function of the coumarin derivatives in gut inflammation using an infectious colitis model. In an in vivo infectious colitis model, administration of selected C1 coumarin derivatives reduced pathogen loads, the number of inflammatory immune cells (Th1 cells and Th17 cells), and inflammatory cytokine levels (IL-6 and IL-1b) in the intestinal tissue after pathogen infection. In addition, we found that the administration of C1 coumarin derivatives minimized abnormal gut microbiome shift-driven pathogen infection. Potential pathogenic gut microbes, such as Enterobacteriaceae and Staphylococcaceae, were increased by pathogen infection. However, this pathogenic microbial expansion was minimized and beneficial bacteria, such as Ligilactobacillus and Limosilactobacillus, increased with C1 coumarin derivative treatment. Functional gene enrichment assessment revealed that the relative abundance of genes associated with lipid and nucleotide metabolism was reduced by pathogen infection; however, this phenomenon was not observed in C1 coumarin derivative-treated animals. Collectively, our data suggest that C1 coumarin derivative is effective antibacterial agents that minimize pathogeninduced gut inflammation and abnormal gut microbiome modulation through their antibacterial activity. [ABSTRACT FROM AUTHOR]

Chronic inflammation is driven by proinflammatory cytokines such as interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), and chemokines, such as c-c motif chemokine ligand 2 (CCL2), CCL3, C-X-C motif chemokine ligand 2 (CXCL2), and CXCL10. Inflammatory processes of the central nervous system (CNS) play an important role in the pathogenesis of various neurological and psychiatric disorders like Alzheimer's disease, Parkinson's disease, and depression. Therefore, identifying novel anti-inflammatory drugs may be beneficial for treating disorders with a neuroinflammatory background. The G-protein-coupled receptor 55 (GPR55) gained interest due to its role in inflammatory processes and possible involvement in different disorders. This study aims to identify the anti-inflammatory effects of the coumarin-based compound KIT C, acting as an antagonist with inverse agonistic activity at GPR55, in lipopolysaccharide (LPS)-stimulated BV2 microglial cells in comparison to the commercial GPR55 agonist O-1602 and antagonist ML-193. All compounds significantly suppressed IL-6, TNF-α, CCL2, CCL3, CXCL2, and CXCL10 expression and release in LPS-treated BV2 microglial cells. The anti-inflammatory effects of the compounds are partially explained by modulation of the phosphorylation of p38 mitogen-activated protein kinase (MAPK), p42/44 MAPK (ERK 1/2), protein kinase C (PKC) pathways, and the transcription factor nuclear factor (NF)-κB, respectively. Due to its potent anti-inflammatory properties, KIT C is a promising compound for further research and potential use in inflammatory-related disorders. [ABSTRACT FROM AUTHOR]

In the title compound, C20H18O4, the dihedral angle between the 2H-chromen-2-one ring system and the phenyl ring is 89.12 (5)°. In the crystal, the molecules are connected through C—H...O hydrogen bonds to generate [010] double chains that are reinforced by weak aromatic π–π stacking interactions. The unit-cell packing can be described as a tilted herringbone motif. The H...H, H...O/O...H, H...C/C...H and C...C contacts contribute 46.7, 24.2, 16.7 and 7.6%, respectively, to its Hirshfeld surface.

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.

In the title compound, C20H18O4, the dihedral angle between the 2H-chromen-2-one ring system and the phenyl ring is 89.12(5)°. In the crystal, the molecules are connected through C--H...O hydrogen bonds to generate [010] double chains that are reinforced by weak aromatic p-p stacking interactions. The unit-cell packing can be described as a tilted herringbone motif. The H...H, H...O/O...H, H...C/C...H and C...C contacts contribute 46.7, 24.2, 16.7 and 7.6%, respectively, to its Hirshfeld surface. [ABSTRACT FROM AUTHOR]

Chronic inflammation is driven by proinflammatory cytokines such as interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), and chemokines, such as c-c motif chemokine ligand 2 (CCL2), CCL3, C-X-C motif chemokine ligand 2 (CXCL2), and CXCL10. Inflammatory processes of the central nervous system (CNS) play an important role in the pathogenesis of various neurological and psychiatric disorders like Alzheimer’s disease, Parkinson’s disease, and depression. Therefore, identifying novel anti-inflammatory drugs may be beneficial for treating disorders with a neuroinflammatory background. The G-protein-coupled receptor 55 (GPR55) gained interest due to its role in inflammatory processes and possible involvement in different disorders. This study aims to identify the anti-inflammatory effects of the coumarin-based compound KIT C, acting as an antagonist with inverse agonistic activity at GPR55, in lipopolysaccharide (LPS)-stimulated BV2 microglial cells in comparison to the commercial GPR55 agonist O-1602 and antagonist ML-193. All compounds significantly suppressed IL-6, TNF-α, CCL2, CCL3, CXCL2, and CXCL10 expression and release in LPS-treated BV2 microglial cells. The anti-inflammatory effects of the compounds are partially explained by modulation of the phosphorylation of p38 mitogen-activated protein kinase (MAPK), p42/44 MAPK (ERK 1/2), protein kinase C (PKC) pathways, and the transcription factor nuclear factor (NF)-κB, respectively. Due to its potent anti-inflammatory properties, KIT C is a promising compound for further research and potential use in inflammatory-related disorders.

Neonatal sepsis is a severe bacterial infection that can lead to life-threatening complications in newborns. Pseudomonas extremorientalis is a Gram-negative bacterium and these Gram-negative organisms have been identified as a major cause of neonatal sepsis. The virulence factors produced by this bacterium play a crucial role in its pathogenicity. Therefore, targeting these virulence factors could be a potential strategy to treat neonatal sepsis caused by P. extremorientalis. In this study, we investigated the efficacy of 3-(bromoacetyl) coumarin (3-BC) in reducing the virulence factors of P. extremorientalis strains isolated from neonatal sepsis. Our results showed that 3-BC effectively reduced the production of various virulence factors, including protease, elastase, siderophore, and exopolysaccharide in these strains. Furthermore, at a concentration of 125 µg/ml, 3-BC also inhibited the biofilm formation ability of these strains in combination with ciprofloxacin. It was discovered that 3-BC was functionally effective in protecting C. elegans against bacterial infection. Moreover, the in vitro and in vivo outcomes were strongly correlated with docking studies of various activator proteins. Overall, our findings suggest that 3-BC could be a potential therapeutic agent for the treatment of neonatal sepsis caused by P. extremorientalis. Further studies are needed to explore the mechanism of action of 3-BC and its potential use in clinical settings. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a typical progressive neurodegenerative disorder, and with multiple possible pathogenesis. Among them, coumarin derivatives could be used as potential drugs as monoamine oxidase-B (MAO-B) inhibitors. Our lab has designed and synthesized coumarin derivatives based on MAO-B. In this study, we used nuclear magnetic resonance (NMR)-based metabolomics to accelerate the pharmacodynamic evaluation of candidate drugs for coumarin derivative research and development. We detailed alterations in the metabolic profiles of nerve cells with various coumarin derivatives. In total, we identified 58 metabolites and calculated their relative concentrations in U251 cells. In the meantime, the outcomes of multivariate statistical analysis showed that when twelve coumarin compounds were treated with U251cells, the metabolic phenotypes were distinct. In the treatment of different coumarin derivatives, there several metabolic pathways changed, including aminoacyl-tRNA biosynthesis, D-glutamine and D-glutamate metabolism, glycine, serine and threonine metabolism, taurine and hypotaurine metabolism, arginine biosynthesis, alanine, aspartate and glutamate metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, glutathione metabolism and valine, leucine and isoleucine biosynthesis. Our work documented how our coumarin derivatives affected the metabolic phenotype of nerve cells in vitro. We believe that these NMR-based metabolomics might accelerate the process of drug research in vitro and in vivo. [ABSTRACT FROM AUTHOR]

In this work, a coumarin derivative, SWJT-14, was synthesized as a fluorescence probe to distinguish cysteine (Cys), homocysteine (Hcy) and glutathione (GSH) in aqueous solutions. The detection limit of Cys, Hcy and GSH for the probe was 0.02 μM, 0.42 μM and 0.92 μM, respectively, which was lower than biothiols in cells. The probe reacted with biothiols to generate different products with different conjugated structures. Additionally, it could distinguish Cys, Hcy and GSH using fluorescence and UV-Vis spectra. The detection mechanism was confirmed by MS. SWJT-14 was successfully used in cellular experiments and detected both endogenous and exogenous biothiols. [ABSTRACT FROM AUTHOR]

The cotton leafworm, Spodoptera littoralis Boisd. is a serious pest attacking a wide range of ornamentals and many field crops. It is well documented that some heterocyclic systems have efficient insecticidal activities. So novel hydrazide‐hydrazone namely, N′,N′′′‐((methylenebis(6‐hydroxy‐3,1‐phenylene))bis(methanylylidene))bis(2‐cyanoacetohydrazide) 3 was exploited as a target to synthesize bis‐heterocyclic moieties such as furan, pyridone, coumarin, thiazole and isoxazole, and also some bis‐heteroarylidenes including heterocycles as indole and pyrazole. The chemical structures of the synthesized compounds were established on the basis of elemental analyses and some spectroscopic tools. All the synthesized compounds were screened for the insecticidal efficacy against the 4th larval instar of Spodoptera littoralis (cotton leafworm). Manifestly, the data showed that compounds 9 and 14 possess remarkable potency but the rest of compounds showed no pronounced activity against cotton leafworm. [ABSTRACT FROM AUTHOR]

Cysteine (Cys) is the major intracellular thiol and plays a key role in human pathology. Furthermore, endogenous sulfur dioxide (SO 2) is produced in mammals. Abnormal levels of SO 2 are commonly associated with a variety of respiratory, cardiovascular, and neurological diseases. Therefore, given their important role in life activities, it is significant to construct a fluorescent probe that can detection between Cys and SO 2. We have designed and synthesized a two-site fluorescent probe CUM with coumarin derivative and benzaldehyde molecules, which can detect and differentiate between Cys and SO 2 through dual excitation wavelengths. Its carbon-carbon double bond reacts with Cys and undergoes a nucleophilic reaction, emitting green fluorescence at 520 nm, while SO 3 2− reacts with benzaldehyde molecules in the probe CUM and undergoes a blue fluorescence at 460 nm. SO 3 2− reacts with the benzaldehyde molecule of probe CUM and fluoresces blue at 460 nm. Thus, the probe CUM with two reaction sites can distinguish between Cys and SO 2 and shows good selectivity and fast reaction speed. In addition, we successfully utilized probe CUM to image Cys and SO 2 in human breast cancer cells (MDA-MB-231). This work provides an effective method for the molecular design of coumarin-based fluorescent probes. Probe CUM as a promising and reliable tool for the meticulous discrimination and quantification of Cys and SO 2 in diverse biological matrices, thereby opening up new avenues for various biological systems. [Display omitted] • A novel fluorescent probe CUM for simultaneous detection of Cys and SO 2. • The probe with two reaction sites shows good selectivity and fast reaction speed. • The probe enables imaging of Cys and SO 2 in human breast cancer cells (MDA-MB-231). [ABSTRACT FROM AUTHOR]

The white spot syndrome virus (WSSV) causes white spot disease (WSD), a severe condition in crustacean aquaculture, leading to significant economic losses. Our previous study demonstrated that C7 is an effective therapeutic agent against WSSV infection in aquaculture. It specifically blocked viral horizontal transmission and reduced shrimp mortality in a dose- and time-dependent manner. Here, we report the potential antiviral mechanism of C7 in shrimp. C7 regulated abnormal glycerophospholipid metabolism caused by WSSV and inhibited phosphatidylcholine (PC) synthesis by more than twofold, potentially enhancing shrimp resistance to viral infection. As the primary phospholipid in the cell membrane, PC is one of the main reactants in lipid peroxidation. Our results indicated that C7 significantly reduced the levels of lipid peroxidation products 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA) induced by WSSV, whereas PC had the opposite effect. Accumulation of lipid peroxidation products inhibits stimulator of interferon genes (STING) signaling. Further evidence showed that C7 promoted STING transport from the endoplasmic reticulum to the Golgi apparatus, significantly activating the expression of the shrimp interferon analogue Vago4 gene. In contrast, PC suppressed Vago4 expression. Our results demonstrated that C7 inhibited PC synthesis, reduced the degree of lipid peroxidation, promoted STING translocation, activated Vago4 expression, and ultimately exerted antiviral effects. Therefore, C7 exhibits immunoregulatory activity as a preventative agent for enhancing the innate immunity of shrimp, making it potentially useful for future immunomodulatory approaches. • C7 significantly reduces phosphatidylcholine (PC) levels in WSSV-infected shrimp. • Exogenous PC promotes WSSV infection, suggesting that PC modulation is crucial for the antiviral activity of C7. • C7 promotes the transport of STING, triggering the innate immune gene Vago4 , thereby exerting anti-WSSV effects. [ABSTRACT FROM AUTHOR]

Abstract Background Depression is one of the most common mental illnesses worldwide. Nitric oxide (NO) is involved in the pathophysiology of depression. Auraptene (a coumarin derivative) has been shown to possess pharmacological effects on neurological diseases. Purpose The present study aimed to investigate the possible role of the NO pathway in Auraptene antidepressant effects in male mice. Methods Behavioral tests were used to assess depression-like behaviors. The mice received Auraptene at 10, 30, and 100 mg/kg, the combination of the sub-effective (ineffective) dose of Auraptene (10 mg/kg) and L-NAME, and the combination of the effective dose of Auraptene (30 mg/kg) and L-arginine. Finally, OFT, TST, FST, brain, serum MDA level, antioxidant capacity, hippocampus, and serum NO level were measured. Results The data analysis showed that Auraptene (30 mg/kg) improved depression-like behaviors. Auraptene (30 mg/kg) also significantly reduced serum NO levels (P

Breast cancer, a heterogeneous disease, is among the most frequently diagnosed diseases and is the second leading cause of death due to cancer among women after lung cancer. Phytoactives (plant-based derivatives) and their derivatives are safer than synthetic compounds in combating chemoresistance. In the current work, a template-based design of the coumarin derivative was designed to target the ADP-sugar pyrophosphatase protein. The novel coumarin derivative (2R)-2-((S)-sec-butyl)-5-oxo-4-(2-oxochroman-4-yl)-2,5-dihydro-1H-pyrrol-3-olate was designed. Molecular docking studies provided a docking score of −6.574 kcal/mol and an MM-GBSA value of −29.15 kcal/mol. Molecular dynamics simulation studies were carried out for 500 ns, providing better insights into the interaction. An RMSD change of 2.4 Å proved that there was a stable interaction and that there was no conformational change induced to the receptor. Metadynamics studies were performed to calculate the unbinding energy of the principal compound with NUDT5, which was found to be −75.171 kcal/mol. In vitro validation via a cytotoxicity assay (MTT assay) of the principal compound was carried out with quercetin as a positive control in the MCF7 cell line and with an IC50 value of 55.57 (+/−) 0.7 μg/mL. This work promoted the research of novel natural derivatives to discover their anticancer activity. [ABSTRACT FROM AUTHOR]

The novel compound 4-methyl-7-((2-((5-methyl-1,3,4-thiadiazol-2-yl)thio)ethyl)thio)-coumarin is obtained in good yield via a two-step protocol; that is, initial synthesis of the reagent 2-((2-chloroethyl)thio)-5-methyl-1,3,4-thiadiazole followed by alkylation of 7-mercapto-4-methylcoumarin. The product's structure is assigned by 1D and 2D NMR experiments and is confirmed by single-crystal XRD. [ABSTRACT FROM AUTHOR]

The novel compound 4-methyl-7-((2-((5-methyl-1,3,4-thiadiazol-2-yl)thio)ethyl)thio)-coumarin is obtained in good yield via a two-step protocol; that is, initial synthesis of the reagent 2-((2-chloroethyl)thio)-5-methyl-1,3,4-thiadiazole followed by alkylation of 7-mercapto-4-methylcoumarin. The product’s structure is assigned by 1D and 2D NMR experiments and is confirmed by single-crystal XRD.

Six coumarin derivatives including two new, 2-acetyl-4-hydroxy-6 H -furo[2,3- g ]chromen-6-one (1) and 2-(1',2'-dihydroxypropan-2'-yl)-4-hydroxy-6 H -furo[2,3- g ]chromen-6-one (2), and four known ones, 7 H -furo [3,2- g ][1]benzopyran-7-one (3), esculetin (4), isoscopoletin (5) and 7,8-dihydroxy-6-methoxycoumarin (6), were isolated for the first time from the whole plant of Spermacoce latifolia. Their structures were determined by detailed spectroscopic analysis and comparison with literature reported data. In vitro antibacterial assay indicated that compounds 1 , 2 and 4 were active toward bacteria Staphyloccocus aureus , Bacillus subtilis and Bacillus cereus with MIC values ranging from 7.81 to 62.5 ug/mL. [Display omitted] • Two new coumarin derivatives (1 and 2) were isolated from Spermacoce latifolia. • Four known compounds (3 − 6) were also obtained from S. latifolia for the first time. • The structures of the isolated compounds were elucidated by spectroscopic means. • Compounds 1 , 2 and 4 showed moderate or slight antibacterial activity. [ABSTRACT FROM AUTHOR]

Coumarins and their derivatives are becoming a potential source for new drug discovery due to their vast array of biological activities. The present study was designed to investigate the cardioprotective effects of a newly synthesised coumarin, symbolised as 5,6‐PhSHC, against cardiac remodelling process in isoproterenol (ISO) induced myocardial infarction (MI) in male Wistar rats by evaluating haematological, biochemical and cardiac biomarkers. Rats were pre/co‐treated with 5,6‐PhSHC or clopidogrel (150 μg/kg body weight) daily for a period of 7 days and then MI was induced by injecting ISO (85 mg/kg body weight), at an interval of 24 hours for 2 consecutive days, on the sixth and seventh days. The in vivo exploration indicated that the injection of 5,6‐PhSHC improved the electrocardiographic (ECG) pattern and prevented severe heart damage by reducing leakage of the cardiac injury markers, such as troponin‐T (cTn‐T), lactate dehydrogenase (LDH), and creatine kinase‐MB. The cellular architecture of cardiac sections, altered in the myocardium of infracted rats, was reversed by 5,6‐PhSHC treatment. Results showed that injection of 5,6‐PhSHC elicited significant cardioprotective effects by prevention of myocardium cell necrosis and inflammatory cells infiltration, along with marked decrease in plasma levels of fibrinogen. In addition, the total cholesterol, triglyceride, LDL‐c, and HDL profiles underwent remarkable beneficial changes. It was also interesting to note that 5,6‐PhSHC enhanced the antioxidative defence mechanisms by increasing myocardial glutathione (GSH) level, superoxide dismutase (SOD), and catalase (CAT) activities, together with reducing the levels of thiobarbituric‐acid‐reactive substances (TBARS), when compared with ISO‐induced rats. Taken together, these findings suggested a beneficial role for 5,6‐PhSHC against ISO‐induced MI in rats. Furthermore, in silico analysis showed that 5,6‐PhSHC possess high computational affinities (E‐value >−9.0 kcal/mol) against cyclooxygenase‐2 (PDB‐ID: 1CX2), vitamin K epoxide reductase (PDB‐ID: 3KP9), glycoprotein‐IIb/IIIa (PDB‐ID: 2VDM) and catalase (PDB‐ID: 1DGF). Therefore, the present study provided promising data that the newly synthesised coumarin can be useful in the design and synthesis of novel drug against myocardial infarction. [ABSTRACT FROM AUTHOR]

• Four compounds XOT1 - XOT4 with different terminal groups were synthesized using triphenylamine and coumarin as the main substituents. • The fluorescence intensity of XOT1 - XOT4 exhibited a good linear correlation with polarity. • Among them, XOT3 with ester group can effectively monitor changes in LDs polarity during apoptosis and ferroptosis process. • XOT3 could be effectively utilized for visualizing intracellular LDs without requiring any washing steps. • XOT3 was capable of effectively visualizing LDs in tissues and organs in mouse models of NAFLD. Aberrant alterations in the polarity of lipid droplets (LDs) are closely linked to disorders of lipid metabolism, which can result in LDs dysfunction and the onset of various diseases, including non-alcoholic fatty liver disease (NAFLD) and specific types of cancer. Therefore, it is imperative to comprehensively comprehend and accurately diagnose associated diseases by monitoring changes in LDs polarity in real time. In this paper, we designed and synthesized four novel fluorescent probes XOT1 - XOT4 by using coumarin as a polarity-sensitive group and incorporate various triphenylamine derivatives as electron-donating groups, enabling specific targeting of LDs. All four probes possess high sensitivity towards minute polarity changes. Among them, XOT3 exhibited excellent photophysical properties and demonstrated a linear fluorescence change (R 2 = 0.98596) within the polarity range of Δ f = 0.023496 ∼ 0.047464. Moreover, probe XOT3 could be effectively utilized for visualizing intracellular LDs by precisely targeting them without requiring any washing steps. Importantly, probe XOT3 has been successfully utilized to monitor alterations in the polarity of LDs during apoptosis and ferroptosis as well as the quantity, size, and fluorescence intensity of LDs stimulated by oleic acid. Furthermore, probe XOT3 was capable of effectively visualizing LDs in tissues and organs in mouse models of non-alcoholic fatty liver disease (NAFLD), which provides a powerful tool for the early diagnosis of NAFLD. [Display omitted] [ABSTRACT FROM AUTHOR]

Viral hemorrhagic septicemia virus (VHSV) poses a significant threat to global aquaculture, prompting ongoing efforts to identify potential drug candidates for disease prevention. Coumarin derivatives have recently emerged as a promising class of compounds effective against rhabdoviruses, which severely impact the aquaculture industry. In this study, we assessed the anti-VHSV activity of umbelliferone (7-hydroxycoumarin) in fathead minnow (FHM) cells and olive flounder Paralichthys olivaceus. Umbelliferone exhibited an EC 50 of 100 μg/mL by reducing cytopathic effect, with a maximum cytotoxicity of 30.9 % at 750 μg/mL. Mechanistic analyses via a time-course plaque reduction assay revealed that direct incubation with the virus for 1 h resulted in 97.0 ± 1.8 % plaque reduction, showing excellent direct virucidal activity. Pretreatment for 4 h resulted in a 33.5 ± 7.8 % plaque reduction, which increased with longer incubation times. Cotreatment led to a 33.5 ± 2.9 % plaque reduction, suggesting interference with viral binding, whereas postinfection treatment proved less effective. Umbelliferone was prophylactically administered to the olive flounder through short-term (3 days) and long-term (14 days) medicated feeding, followed by a 4-day postinfection period. Short-term administration at 100 mg/kg body weight (bw)/day resulted in the highest relative percent survival (RPS) of 56 %, whereas long-term administration achieved a maximum RPS of 44 % at 30 mg/kg bw/day. Umbelliferone administration delayed mortality at these doses. Additionally, umbelliferone significantly inhibited the expression of the VHSV N gene during viral challenge, with no observed toxic effects in fish up to an administration dose of 30 mg/kg bw/day for 28 days. Our findings suggest that the protective mechanism of short-term administration of 100 mg umbelliferone against VHSV infection may involve the overexpression of TLR2, MDA5, STAT1, and NF-κB at 24 h postinfection (hpi). IL-8 and IFN II expression was upregulated, whereas TNF-α, IL-1β, and IFN I expression was suppressed at 24 hpi. The upregulation of ISG15 at 48 hpi may contribute to the inhibition of VHSV replication, whereas the downregulation of Caspase 3 expression at 96 hpi suggests a possible inhibition of virus-induced apoptosis at later infection stages. Overall, umbelliferone exhibited anti-VHSV activity through multiple mechanisms, with the added advantage of convenient administration via medicated feed. • Umbelliferone exhibits strong direct virucidal activity against VHSV. • Umbelliferone-medicated feed prevents VHS in olive flounder. • The anti-VHSV effects occur via TNF-α, IL-1β, IFN I, and caspase 3 inhibition. • Antiviral effects were also linked to IL-8, IFN II, and ISG15 upregulation. [ABSTRACT FROM AUTHOR]

Background: Depression is one of the most common mental illnesses worldwide. Nitric oxide (NO) is involved in the pathophysiology of depression. Auraptene (a coumarin derivative) has been shown to possess pharmacological effects on neurological diseases. Purpose: The present study aimed to investigate the possible role of the NO pathway in Auraptene antidepressant effects in male mice. Methods: Behavioral tests were used to assess depression-like behaviors. The mice received Auraptene at 10, 30, and 100 mg/kg, the combination of the sub-effective (ineffective) dose of Auraptene (10 mg/kg) and L-NAME, and the combination of the effective dose of Auraptene (30 mg/kg) and L-arginine. Finally, OFT, TST, FST, brain, serum MDA level, antioxidant capacity, hippocampus, and serum NO level were measured. Results: The data analysis showed that Auraptene (30 mg/kg) improved depression-like behaviors. Auraptene (30 mg/kg) also significantly reduced serum NO levels (P < 0.05) and significantly increased serum MDA (10 mg/kg, P < 0.05). Auraptene at 30 mg/kg also increased serum antioxidant capacity (P < 0.01). Co-administration of L-NAME and the sub-effective dose of Auraptene enhanced the effects of Auraptene. However, co-administration of the effective dose of Auraptene and L-arginine reduced the impacts of Auraptene. Conclusions: The results showed that Auraptene causes antidepressant effects in a dose-dependent manner and acts as a prooxidant at 100 mg/kg, and exacerbates oxidative stress. The antidepressant effects of this active molecule are exerted by reducing the NO level in the hippocampus and serum, increasing the antioxidant capacity, and reducing the MDA level in the serum. [ABSTRACT FROM AUTHOR]

In recent times, the crime rate is increasing in the society, and the maintaining of criminal records is becoming essential by locating and tracking each case through latent fingerprint identification along with the imperative of finding the intensity and wavelength via Aggregation Induced Emission (AIE). To meet these demands, we have designed a novel AIE based electron withdrawing moiety such as 2-(4-fluorophenyl)-3H-benzocoumarin. This Coumarin Fluorescent Tag (CFT) was synthesized with the aid of ultra-sonic waves. Fluorescence properties of the CFT were characterized by photoluminescence (PL). The Fluoro functional groups of CFT produce pale-blue emission in solid as well as the liquid state. An in-depth examination of latent fingerprints (LFPs) showed unchangeable and everlasting patterns due to the strong adsorption of CFT on the ridges of the finger under visible and 365 nm UV light. This imaging of such strong ridges becomes a crucial element in forensic applications. In addition to check the AIE properties, the newly designed CFT was investigated using PL Instrument and UV chamber.

Abstract Background Columbianadin (CBN) is one of the main coumarin constituents isolated from Angelica pubescens. The pharmacological value of CBN is well demonstrated, especially in the prevention of several cancers and analgesic activity. A striking therapeutic target for arterial thrombosis is inhibition of platelet activation because platelet activation significantly contributes to these diseases. The current study examined the influence of CBN on human platelet activation in vitro and vascular thrombotic formation in vivo. Methods Aggregometry, immunoblotting, immunoprecipitation, confocal microscopic analysis, fibrin clot retraction, and thrombogenic animals were used in this study. Results CBN markedly inhibited platelet aggregation in washed human platelets stimulated only by collagen, but was not effective in platelets stimulated by other agonists such as thrombin, arachidonic acid, and U46619. CBN evidently inhibited ATP release, intracellular ([Ca2+]i) mobilization, and P-selectin expression. It also inhibited the phosphorylation of phospholipase C (PLC)γ2, protein kinase C (PKC), Akt (protein kinase B), and mitogen-activated protein kinases (MAPKs; extracellular signal-regulated kinase [ERK] 1/2 and c-Jun N-terminal kinase [JNK] 1/2, but not p38 MAPK) in collagen-activated platelets. Neither SQ22536, an adenylate cyclase inhibitor, nor ODQ, a guanylate cyclase inhibitor, reversed the CBN-mediated inhibition of platelet aggregation. CBN had no significant effect in triggering vasodilator-stimulated phosphoprotein phosphorylation. Moreover, it markedly hindered integrin αIIbβ3 activation by interfering with the binding of PAC-1; nevertheless, it had no influences on integrin αIIbβ3-mediated outside-in signaling such as adhesion number and spreading area of platelets on immobilized fibrinogen as well as thrombin-stimulated fibrin clot retraction. Additionally, CBN did not attenuate FITC-triflavin binding or phosphorylation of proteins, such as integrin β3, Src, and focal adhesion kinase, in platelets spreading on immobilized fibrinogen. In experimental mice, CBN increased the occlusion time of thrombotic platelet plug formation. Conclusion This study demonstrated that CBN exhibits an exceptional activity against platelet activation through inhibition of the PLCγ2-PKC cascade, subsequently suppressing the activation of Akt and ERKs/JNKs and influencing platelet aggregation. Consequently, this work provides solid evidence and considers that CBN has the potential to serve as a therapeutic agent for the treatment of thromboembolic disorders.

Alzheimer’s disease (AD) is a typical progressive neurodegenerative disorder, and with multiple possible pathogenesis. Among them, coumarin derivatives could be used as potential drugs as monoamine oxidase-B (MAO-B) inhibitors. Our lab has designed and synthesized coumarin derivatives based on MAO-B. In this study, we used nuclear magnetic resonance (NMR)-based metabolomics to accelerate the pharmacodynamic evaluation of candidate drugs for coumarin derivative research and development. We detailed alterations in the metabolic profiles of nerve cells with various coumarin derivatives. In total, we identified 58 metabolites and calculated their relative concentrations in U251 cells. In the meantime, the outcomes of multivariate statistical analysis showed that when twelve coumarin compounds were treated with U251cells, the metabolic phenotypes were distinct. In the treatment of different coumarin derivatives, there several metabolic pathways changed, including aminoacyl-tRNA biosynthesis, D-glutamine and D-glutamate metabolism, glycine, serine and threonine metabolism, taurine and hypotaurine metabolism, arginine biosynthesis, alanine, aspartate and glutamate metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, glutathione metabolism and valine, leucine and isoleucine biosynthesis. Our work documented how our coumarin derivatives affected the metabolic phenotype of nerve cells in vitro. We believe that these NMR-based metabolomics might accelerate the process of drug research in vitro and in vivo.

In this work, a coumarin derivative, SWJT-14, was synthesized as a fluorescence probe to distinguish cysteine (Cys), homocysteine (Hcy) and glutathione (GSH) in aqueous solutions. The detection limit of Cys, Hcy and GSH for the probe was 0.02 μM, 0.42 μM and 0.92 μM, respectively, which was lower than biothiols in cells. The probe reacted with biothiols to generate different products with different conjugated structures. Additionally, it could distinguish Cys, Hcy and GSH using fluorescence and UV-Vis spectra. The detection mechanism was confirmed by MS. SWJT-14 was successfully used in cellular experiments and detected both endogenous and exogenous biothiols.

A preliminary phytochemical investigation of the stems of the endangered plant Ulmus elongata led to the isolation of a new coumarin derivative (named ulmuselactone A, 1) and eight known compounds (2-9). The new structure was elucidated by detailed analysis of comprehensive spectroscopic methods, and its absolute configuration was established by comparing experimental and calculated electronic circular dichroism (ECD) spectra. The isolated compounds were evaluated for their antibacterial activities. [ABSTRACT FROM AUTHOR]

Breast cancer, a heterogeneous disease, is among the most frequently diagnosed diseases and is the second leading cause of death due to cancer among women after lung cancer. Phytoactives (plant-based derivatives) and their derivatives are safer than synthetic compounds in combating chemoresistance. In the current work, a template-based design of the coumarin derivative was designed to target the ADP-sugar pyrophosphatase protein. The novel coumarin derivative (2R)-2-((S)-sec-butyl)-5-oxo-4-(2-oxochroman-4-yl)-2,5-dihydro-1H-pyrrol-3-olate was designed. Molecular docking studies provided a docking score of −6.574 kcal/mol and an MM-GBSA value of −29.15 kcal/mol. Molecular dynamics simulation studies were carried out for 500 ns, providing better insights into the interaction. An RMSD change of 2.4 Å proved that there was a stable interaction and that there was no conformational change induced to the receptor. Metadynamics studies were performed to calculate the unbinding energy of the principal compound with NUDT5, which was found to be −75.171 kcal/mol. In vitro validation via a cytotoxicity assay (MTT assay) of the principal compound was carried out with quercetin as a positive control in the MCF7 cell line and with an IC50 value of 55.57 (+/−) 0.7 μg/mL. This work promoted the research of novel natural derivatives to discover their anticancer activity.

Viral hemorrhagic septicemia virus (VHSV) is one of the most important viruses in the aquaculture of farmed finfish. As there is no single solution to prevent or treat VHSV infection, the role of chemical drugs as candidate antiviral agents is indispensable. In this study, we screened 16 coumarin derivatives against VHSV using fathead minnow (FHM) cells by evaluating the cytotoxicity, the inhibition of the VHSV cytopathic effect (CPE) and VHSV N gene expression, respectively. Scoparone (6,7-dimethoxycoumarin), stood out as the most effective compound against VHSV, showing 103.5 ± 10.2 μg/mL 20% cytotoxicity (CC 20), 40% CPE reduction and 9.8-fold (P < 0.001) VHSV N gene inhibition at 100 μg/mL. Scoparone, at 100 μg/mL inhibited the VHSV infection by 1-h postinfection treatment, with 52.0% ± 17.1% plaque reduction (P < 0.05), and 90.6% VHSV N gene inhibition (P < 0.05) indicating it inhibits viral internalization and replication. Scoparone exhibited direct virucidal activity, increasing with exposure period, up to 32.3% ± 1.3% plaque reduction from 4 h incubation (P < 0.001), indicating its reversible nature. Scoparone-medicated feed protected the fish from VHSV infection, with up to 44% relative percent survival by 1 mg (long-term) and 10 mg (short-term) prophylactic administration per kg body weight (bw) per day for 21 and 7 days, respectively, in the olive flounder Paralichthys olivaceus. No negative effects were noted on the growth, biochemical, or innate immunological parameters of the fish administered up to 3 mg/kg bw/day of scoparone-medicated feed for 28 days. The administration of scoparone-medicated feed at 1 mg/kg bw/day for 14 days and subsequent VHSV challenge decreased VHSV N gene expression by 48 h postinfection (hpi) in olive flounders. Increased expression levels of IFN I and ISG15 suggested the pivotal role of the IFN I system in conferring scoparone-mediated protection against VHSV infection. The activation of MDA5 at 48 hpi must be attributed to the elevated interferon activity. Elevated interferon type II expression levels suggested the induction of adaptive immune responses. The expression of TLR2 was suppressed at 72 hpi, reflecting reduced viral replication by scoparone. The suppressed expression of caspase 3 suggested that scoparone inhibits virus-induced apoptosis. In summary, scoparone can be considered a practical candidate for protecting farmed finfish against VHSV. It can protect olive flounders from VHSV infection through multiple mechanisms of action and by a convenient mode of administration via medicated feed. [Display omitted] • Scoparone inhibits replication of VHSV in vitro and in vivo. • Scoparone has direct virucidal activity against VHSV. • Scoparone-medicated feed has prophylactic effect against VHS in olive flounder. • Scoparone activates IFN I system upon VHS infection. [ABSTRACT FROM AUTHOR]

A coumarin-derived compound, 3-benzoyl-7-hydroxy coumarin (BHYC), is synthesized to determine its optoelectronic properties, including absorbance band edge, optical band gap, transmittance, refractive index, electrical susceptibility, volume-surface energy loss functions and optical/electrical conductance parameters. The absorbance spectra of BHYC in dimethylformamide (DMF) and dimethylsulfoxide (DMSO) solvents exhibit maximum peaks at 350 and 353 nm, respectively, in the near-ultraviolet region. The absorbance band edge values of BHYC in DMF and DMSO are 2.526 and 2.500 eV, respectively. The optical band gap of BHYC varies from 2.560 to 2.408 eV with increasing molarity. In contrast, the refractive index of BHYC increases from 2.47 to 2.95 with changing molarity. The obtained results show that 3-benzoyl-7-hydroxy coumarin exhibits a semiconductor behavior and it may be an important candidate for many optoelectronic devices, such as diodes, photodiodes and sensors.

Coumarin, a phenolic compound, is a secondary metabolite produced by plants such as Tanga and Lime. Coumarin derivatives were prepared via Pechmann condensation. In this study, we performed in vitro and in vivo experiments to determine the antimicrobial and gut immune-regulatory functions of coumarin derivatives. For the in vitro antimicrobial activity assay, coumarin derivatives C1 and C2 were selected based on their pathogen-killing activity against various pathogenic microbes. We further demonstrated that the selected coumarin derivatives disrupted bacterial cell membranes. Next, we examined the regulatory function of the coumarin derivatives in gut inflammation using an infectious colitis model. In an in vivo infectious colitis model, administration of selected C1 coumarin derivatives reduced pathogen loads, the number of inflammatory immune cells (Th1 cells and Th17 cells), and inflammatory cytokine levels (IL-6 and IL-1b) in the intestinal tissue after pathogen infection. In addition, we found that the administration of C1 coumarin derivatives minimized abnormal gut microbiome shift-driven pathogen infection. Potential pathogenic gut microbes, such as Enterobacteriaceae and Staphylococcaceae , were increased by pathogen infection. However, this pathogenic microbial expansion was minimized and beneficial bacteria, such as Ligilactobacillus and Limosilactobacillus , increased with C1 coumarin derivative treatment. Functional gene enrichment assessment revealed that the relative abundance of genes associated with lipid and nucleotide metabolism was reduced by pathogen infection; however, this phenomenon was not observed in C1 coumarin derivative-treated animals. Collectively, our data suggest that C1 coumarin derivative is effective antibacterial agents that minimize pathogen-induced gut inflammation and abnormal gut microbiome modulation through their antibacterial activity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Jung, Park, Gu, Han, Ji, Hwang and Kim.)

Plant disease control mainly relies on pesticides. In this study, a series of coumarin derivatives containing hydrazone moiety were designed and synthesized. The synthesized compounds were characterized and used to evaluate the antifungal activity against four pathogens, Botrytis cinerea, Alternaria solani, Fusarium oxysporum, and Alternaria alternata. The results showed that the inhibition rate of some compounds at 100 μg/mL in 96 hours reached around 70 % against A. alternata, higher than that of the positive control. The corresponding EC 50 values were found at around 30 μg/mL. Finally, the compound 3 b was screened out with the lowest EC 50 value (19.49 μg/mL). The analysis of SEM and TEM confirmed that the compound 3 b can obviously damage the morphological structure of hyphae, resulting in the depletion of the cells by the destruction of morphological matrix and leakage of contents. RNA sequencing showed that compounds 3 b mainly affected the pentose phosphate pathway, which caused to destroy the layer of mitochondrial structure. Molecular docking showed that compounds 3 b fitted the binding pocket of yeast transketolase and interacted with lysine at the hydrazone structure. Our results suggested that the introduction of hydrazone was an effective strategy for the design of novel bioactive compounds., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

New chemotherapeutic agents with minimum side effects are indispensable to treat non–small‐cell lung cancer (NSCLC) since the mortality rate of patients suffering from NSCLC remains high despite receiving conventional medication. In our previous study, many coumarin derivatives were screened for their anticancer properties in A549, an in vitro NSCLC model. One of these, 4‐flourophenylacetamide‐acetyl coumarin (4‐FPAC), induced cytotoxicity at a concentration as low as 0.16 nM. Herein, initially, the cytotoxic potential of 4‐FPAC was tested on a noncancerous cell line NIH3T3 and was found safe at the selected dose of 0.16 nM. Further, we investigated the mechanism by which 4‐FPAC induced cytotoxicity and arrested the progression of cell cycle as well as metastasis in A549. Results of ethidium bromide/acridine orange (EtBr/AO), 4,6‐diamidino‐2‐phenylindole, comet, and lactate dehydrogenase assays revealed that 4‐FPAC caused cytotoxicity via reactive oxygen species‐induced p53‐mediated mechanism, which involves both extrinsic and intrinsic pathways of apoptosis. Dichlorodihydrofluorescein diacetate, rhodamine 123, and AO staining confirmed the involvement of both mitochondria and lysosome in inducing apoptosis. However, flow cytometric analysis revealed that it causes cell cycle arrest at the G0/G1 phase by modulating p21, CDK2, and CDK4 expression. Aggregation, soft‐agar, clonogenic, and scratch assays as well as gene expression analysis collectively confirmed that 4‐FPAC minimizes the metastatic property of A549 by downregulating Snail, matrix metalloproteinase 9, and interleukin‐8. Additional studies reaffirmed the above findings and substantiated the role of PI3K/AKT in achieving them. The cell‐type‐specific selective cytostatic and antimetastatic properties shown by 4‐FPAC indicate its potential to emerge as a drug of choice against NSCLC in the future. [ABSTRACT FROM AUTHOR]

Mercury (Hg) is a heavy metal with high toxicity and easy migration; it can be enriched through the food chain, and cause serious threats to the natural environment and human health. So, the development of a method that can be used to detect mercury ions (Hg2+) in the environment, in cells, and in organisms is very important. Here, a new 7‐hydroxycoumarin‐derived carbonothioate‐based probe (CC‐Hg) was designed and synthesized for detection of Hg2+. After addition of Hg2+, a large fluorescence enhancement was observed due to the formation of 7‐hydroxyl, which reinforced the intramolecular charge transfer process. The CC‐Hg probe had good water solubility and selectivity. Moreover, the probe was able to detect Hg2+ quantitatively over the concentration range 0–2 μM and with a detection limit of 7.9 nM. Importantly, we successfully applied the probe to detect Hg2+ in water samples, in living cells, and in zebrafish. The experimental results demonstrated its potential value in practical applications. [ABSTRACT FROM AUTHOR]

Cancer is one of the most urgent problems in medicine. In recent years, cancer is the second leading cause of death globally. In search for more effective and less toxic treatment against cancer, natural products are used as prototypes in the synthesis of new anticancer drugs. The aim of this study was to investigate the in vivo toxicity and the mechanism of antitumor action of 7-isopentenyloxycoumarin (UMB-07), a coumarin derivative with antitumor activity. The toxicity was evaluated in vitro (hemolysis assay), and in vivo (micronucleus and acute toxicity assays). Ehrlich ascites carcinoma model was used to evaluate in vivo antitumor activity of UMB-07 (12.5, 25, or 50 mg/kg, intraperitoneally, i.p.), after 9 days of treatment, as well as toxicity. UMB-07 (2000 μg/mL) induced only 0.8% of hemolysis in peripheral blood erythrocytes of mice. On acute toxicity assay, LD50 (50% lethal dose) was estimated at around 1000 mg/kg (i.p.), and no micronucleated erythrocytes were recorded after UMB-07 (300 mg/kg, i.p.) treatment. UMB-07 (25 and 50 mg/kg) reduced tumor volume and total viable cancer cells. In the mechanism action investigation, no changes were observed on the cell cycle analysis; however, UMB-07 reduced peritumoral microvessels density and CCL2 chemokine levels. In addition, UMB-07 showed weak toxicity on biochemical, hematological, and histological parameters after 9 days of antitumor treatment. The current findings suggest that UMB-07 has low toxicity and exerts antitumor effect by inhibit angiogenesis via CCL2 chemokine decrease. [ABSTRACT FROM AUTHOR]

Background: Columbianadin (CBN) is one of the main coumarin constituents isolated from Angelica pubescens. The pharmacological value of CBN is well demonstrated, especially in the prevention of several cancers and analgesic activity. A striking therapeutic target for arterial thrombosis is inhibition of platelet activation because platelet activation significantly contributes to these diseases. The current study examined the influence of CBN on human platelet activation in vitro and vascular thrombotic formation in vivo. Methods: Aggregometry, immunoblotting, immunoprecipitation, confocal microscopic analysis, fibrin clot retraction, and thrombogenic animals were used in this study. Results: CBN markedly inhibited platelet aggregation in washed human platelets stimulated only by collagen, but was not effective in platelets stimulated by other agonists such as thrombin, arachidonic acid, and U46619. CBN evidently inhibited ATP release, intracellular ([Ca2+]i) mobilization, and P-selectin expression. It also inhibited the phosphorylation of phospholipase C (PLC)γ2, protein kinase C (PKC), Akt (protein kinase B), and mitogen-activated protein kinases (MAPKs; extracellular signal-regulated kinase [ERK] 1/2 and c-Jun N-terminal kinase [JNK] 1/2, but not p38 MAPK) in collagen-activated platelets. Neither SQ22536, an adenylate cyclase inhibitor, nor ODQ, a guanylate cyclase inhibitor, reversed the CBN-mediated inhibition of platelet aggregation. CBN had no significant effect in triggering vasodilator-stimulated phosphoprotein phosphorylation. Moreover, it markedly hindered integrin αIIbβ3 activation by interfering with the binding of PAC-1; nevertheless, it had no influences on integrin αIIbβ3-mediated outside-in signaling such as adhesion number and spreading area of platelets on immobilized fibrinogen as well as thrombin-stimulated fibrin clot retraction. Additionally, CBN did not attenuate FITC-triflavin binding or phosphorylation of proteins, such as integrin β3, Src, and focal adhesion kinase, in platelets spreading on immobilized fibrinogen. In experimental mice, CBN increased the occlusion time of thrombotic platelet plug formation. Conclusion: This study demonstrated that CBN exhibits an exceptional activity against platelet activation through inhibition of the PLCγ2-PKC cascade, subsequently suppressing the activation of Akt and ERKs/JNKs and influencing platelet aggregation. Consequently, this work provides solid evidence and considers that CBN has the potential to serve as a therapeutic agent for the treatment of thromboembolic disorders. [ABSTRACT FROM AUTHOR]

A novel coumarin derivative CTT was synthesized via the condensation of 7‐(N,N‐diethylamino) coumarin‐3‐aldehyde with 5‐amino‐1,3,4‐thiadiazole‐2‐thiol and its structure was characterized using infrared spectroscopy (IR), 1H NMR, mass spectrometry (MS) techniques, and elemental analysis. The recognition properties of CTT with metal ions were investigated in CH3CN–H2O (v/v = 1/1) solution using UV–vis absorption and fluorescence emission spectrum method. The results showed that CTT could monitor Cu2+ and Hg2+ simultaneously as a dual‐function chemosensor in CH3CN–H2O (v/v = 1/1). CTT could be used to detect Cu2+ colorimetrically; when using CTT, a color change from yellowish‐brown to yellowish‐green could be readily observed by the naked eye. CTT showed turn‐on fluorescent recognition of Hg2+, the fluorescence enhancement was attributed to the inhibited C=N isomerization and the obstructed excited state intramolecular proton transfer (ESIPT) of CTT. The recognition mechanism of CTT for Cu2+ and Hg2+ was studied by experiments and theoretical calculations, respectively. Therefore, CTT has the ability to be a "single chemosensor for dual targets." [ABSTRACT FROM AUTHOR]

A series of coumarin derivatives and isosteres were synthesized from the reaction of triflic intermediates with phenylboronic acids, terminal alkynes, and organozinc compounds through palladium-catalyzed cross-coupling reactions. The in vitro cytotoxic effect of the compounds was evaluated against two non-small cell lung carcinoma (NSCLC) cell lines (A-549 and H2170) and a normal cell line (NIH-3T3) using cisplatin as a reference drug. Additionally, the effects of the most promising coumarin derivative (9f) in reversing the epithelial-to-mesenchymal transition (EMT) in IL-1β-stimulated A549 cells and in inhibiting the EMT-associated migratory ability in A549 cells were also evaluated. 9f had the greatest cytotoxic effect (CC50 = 7.1 ± 0.8 and 3.3 ± 0.5 μM, respectively against A549 and H2170 cells) and CC50 value of 25.8 µM for NIH-3T3 cells. 9f inhibited the IL-1β-induced EMT in epithelial cells by inhibiting the F-actin reorganization, attenuating changes in the actin cytoskeleton reorganization, and downregulating vimentin in A549 cells stimulated by IL-1β. Treatment of A549 cells with 9f at 7 µM for 24 h significantly reduced the migration of IL-1β-stimulated cells, which is a phenomenon confirmed by qualitative assessment of the wound closure. Taken together, our findings suggest that coumarin derivatives, especially compound 9f, may become a promising candidate for lung cancer therapy, especially in lung cancer promoted by NSCLC cell lines.

Synthesis, spectral characterization, and evaluation of in vitro antioxidant activity of a new coumarin derivative, 4- ((1,3,4-thiadiazol-2-yl)amino)-3-nitro-2H-chromene-2-one, are described. The synthesis of the new product was performed in three reaction steps, with a good overall yield (78%). The structure was corroborated by detailed spectral analysis, including the 1D and 2D NMR experiments (1H- and 13C NMR; 1H-1H COSY, NOESY, HSQC, and HMBC). The in vitro antioxidant activity was evaluated using the DPPH test. The synthesized compound possesses a good free-radical scavenging activity, IC50=596.7±0.3 μg/ml, and can serve as a model for the synthesis of similar compounds with promising antioxidant effects.

Two new coumarin derivatives containing phenothiazine or phenoxazine moiety, 3-(benzo[d]oxazol-2-yl)-7-(10H-phenoxazin-10-yl)coumarin (PXZ-C) and 3-(benzo[d]oxazol-2-yl)-7-(10H-phenothiazin-10-yl)coumarin (PTZ-C), were synthesized and characterized by elemental analysis, NMR spectroscopy, and MS. Their photophysical and electrochemical properties and thermal stabilities were investigated systematically. The results showed that these compounds have good thermal stability. The compound PTZ-C exhibits weak blue–green emission upon ultraviolet light excitation, whereas the compound PXZ-C displays weak blue emission. [ABSTRACT FROM AUTHOR]

Coumarin derivatives are a class of natural compounds with phenylhydrazine α-pyrone structure. They exhibit a broad scope of medical (e.g., anticancer, antibacterial, antiinflammatory and antioxidant activities) and pesticidal activities (e.g., insecticidal and antifungal activities). Recent studies have shown that coumarin compounds have the potential to become novel acaricides because of their prominent acaricidal activities and unique target. In this review, the advances on insecticidal, acaricidal, antibacterial activities of coumarin derivatives have been summarized. The structural modification and structure-activity relationship of coumarin derivatives and the acaricidal mechanism of scopoletin against Tetranychus cinnabarinus have also been reviewed. The main target has been identified as the calcium channel-associated G-protein coupled neuropeptide receptor (TcGPCR). These advances provide an important basis for the development of new phytochemical insecticidal and acaricidal agents derived from coumarin and targeting calcium ion channels. [ABSTRACT FROM AUTHOR]

A coumarin-derived compound, 3-benzoyl-7-hydroxy coumarin (BHYC), is synthesized to determine its optoelectronic properties, including absorbance band edge, optical band gap, transmittance, refractive index, electrical susceptibility, volume-surface energy loss functions and optical/electrical conductance parameters. The absorbance spectra of BHYC in dimethylformamide (DMF) and dimethylsulfoxide (DMSO) solvents exhibit maximum peaks at 350 and 353 nm, respectively, in the nearultraviolet region. The absorbance band edge values of BHYC in DMF and DMSO are 2.526 and 2.500 eV, respectively. The optical band gap of BHYC varies from 2.560 to 2.408 eV with increasing molarity. In contrast, the refractive index of BHYC increases from 2.47 to 2.95 with changing molarity. The obtained results show that 3-benzoyl-7-hydroxy coumarin exhibits a semiconductor behavior and it may be an important candidate for many optoelectronic devices, such as diodes, photodiodes and sensors. [ABSTRACT FROM AUTHOR]

Abstract An excellent fluorescent probe with "turn on" phenomenon for sensitive monitoring hypochlorite (ClO−) was prepared using the mild condensation reaction between coumarin and hydroxylamine (NH 2 OH). The probe possessed potent selectivity to ClO− with obvious color changes from yellow to light yellow and green to blue fluorescence emission, which could be noticed by the naked eye. Moreover, the probe has been succeeded in imaging ClO− in living A549 cells and thus has the potential prospect in the visual detection of intracellular ClO−. Graphical abstract Image 1 Highlights • Observable colorimetric and fluorometric changes. • Fast response time. • Highly selective and sensitive response to ClO−. • Strong contrast imaging in living cells. [ABSTRACT FROM AUTHOR]