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BACKGROUND: Scopoletin and umbelliferone belong to coumarins, which are plant specialized metabolites with potent and wide biological activities, the accumulation of which is induced by various environmental stresses. Coumarins have been detected in various plant species, including medicinal plants and the model organism Arabidopsis thaliana. In recent years, key role of coumarins in maintaining iron (Fe) homeostasis in plants has been demonstrated, as well as their significant impact on the rhizosphere microbiome through exudates secreted into the soil environment. Several mechanisms underlying these processes require clarification. Previously, we demonstrated that Arabidopsis is an excellent model for studying genetic variation and molecular basis of coumarin accumulation in plants. RESULTS: Here, through targeted metabolic profiling and gene expression analysis, the gene-metabolite network of scopoletin and umbelliferone accumulation was examined in more detail in selected Arabidopsis accessions (Col-0, Est-1, Tsu-1) undergoing different culture conditions and characterized by variation in coumarin content. The highest accumulation of coumarins was detected in roots grown in vitro liquid culture. The expression of 10 phenylpropanoid genes (4CL1, 4CL2, 4CL3, CCoAOMT1, C3'H, HCT, F6'H1, F6'H2,CCR1 and CCR2) was assessed by qPCR in three genetic backgrounds, cultured in vitro and in soil, and in two types of tissues (leaves and roots). We not only detected the expected variability in gene expression and coumarin accumulation among Arabidopsis accessions, but also found interesting polymorphisms in the coding sequences of the selected genes through in silico analysis and resequencing. CONCLUSIONS: To the best of our knowledge, this is the first study comparing accumulation of simple coumarins and expression of phenylpropanoid-related genes in Arabidopsis accessions grown in soil and in liquid cultures. The large variations we detected in the content of coumarins and gene expression are genetically determined, but also tissue and culture dependent. It is particularly important considering that growing plants in liquid media is a widely used technology that provides a large amount of root tissue suitable for metabolomics. Research on differential accumulation of coumarins and related gene expression will be useful in future studies aimed at better understanding the physiological role of coumarins in roots and the surrounding environments.
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Arabidopsis , Escopoletina , Umbeliferonas , Arabidopsis/genética , Arabidopsis/metabolismo , Escopoletina/metabolismo , Umbeliferonas/metabolismo , Glicósidos/metabolismo , Regulación de la Expresión Génica de las Plantas , Genes de Plantas , Raíces de Plantas/metabolismo , Raíces de Plantas/genética , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismoRESUMEN
INTRODUCTION: Cyclophosphamide (CP), which is a commonly used chemotherapy drug, can lead to a range of side effects such as immunosuppression, bone marrow suppression, leukopenia, and oxidative stress. This study aims to explore the effects of Auraptene (AUR), which has immunomodulatory and antioxidant properties, on immune function in mice that are experiencing suppression induced by CP. MATERIALS AND METHODS: The experiment involved 60 male BALB/c mice that underwent a 10-day treatment. On days 1, 3, and 9, CP was given at 80 mg/kg IP doses to induce immunosuppression. The mice were divided into five groups: Control group, CP group, CP + liposomal AUR 0.2 mg/kg (AUR 0.2), CP + liposomal AUR 0.25 mg/kg (AUR 0.25), and liposomal vehicle group. Various parameters were measured, including mouse weight, immune organ weight index (spleen and thymus), spleen and thymus histopathology, levels of inflammatory cytokines (IL2, IL10, IL4, IFN-γ), TH1/TH2 balance ratio, IgG and IgM immunoglobulin levels, white blood cell count, platelets, neutrophils, lymphocytes, and oxidative activity measured by MDA, SOD, and Total Antioxidant. RESULTS: In the group treated with CP, the mice showed a significant decrease in weight compared to the control group. In contrast, the group treated with AUR maintained their weight and did not show a significant difference from the control group. AUR 0.25 reduced the damage to the spleen and thymus caused by CP. Additionally, AUR 0.25 demonstrated a significant decrease in IL4 and IL10 levels compared to the CP group (p = 0.04), approaching the levels of the control group. Furthermore, IL2 and IFN-γ levels in the AUR 0.25 group significantly increased (p = 0.04) compared to the CP group, reaching levels similar to the control group. AUR also increased serum IgM and IgG levels two to three times compared to the CP group, approaching the levels of the control group. MDA levels in the AUR 0.25 group decreased to normal and control levels. AUR 0.25 also showed increased SOD and Total Antioxidant levels. Additionally, white blood cells, platelets, neutrophils, and lymphocytes in the AUR group significantly increased compared to the CP group, reaching normal levels similar to the control group. The TH1/TH2 ratio in the AUR group exhibited a significant increase of two and a half times (p = 0.002) compared to the CP group. CONCLUSION: These results show that AUR protects against the side effects of CP by increasing the function of the humoral and cellular immune system through the balance of TH1/TH2 and increasing the level of immunoglobulins, as well as increasing the antioxidant activity and the protective role of cytotoxicity.
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BACKGROUND: The Ferluago W.D.J. Koch genus includes 48 accepted perennial herbs that are distributed in the Mediterranean region, Southeast Europe, Central and Middle East of Asia. These plants are widely used in folk and conventional medicine due to their biological benefits such as anti-microbial, anti-inflammatory, anti-cancer, and immunomodulatory properties. Conducting a comprehensive review based on the structure activity relationships (SARs) of the coumarins, which has not been previously documented, can lead to a better insight into the genus Ferulago and its beneficial therapeutic activities. METHODS: This review covers literature from 1969 to 2023, were collected from various scientific electronic databases to review phytochemical, pharmacological, and ethnopharmacological data of Ferulago species, as well as latest information on the SAR of reported coumarins from this genus. RESULTS: Phytochemical studies showed that the biological actions of this genus are mediated by the reported specialized metabolites, such as coumarins and flavonoids. Simple coumarins, prenylated coumarins, furanocoumarins, and pyranocoumarins are the largest subclasses of coumarins found in diverse Ferulago species, which have discussed the biological effects of them with a focus on the Structure-Activity Relationship (SAR). For example, prenylated coumarins have shown potential leishmanicidal and anti-neuropsychiatric effects when substituted with a prenyl group at the 7-hydroxy, as well as the C6 and C8 positions in their scaffold. Similarly, furanocoumarins exhibit varied biological activities such as anti-inflammatory, anti-proliferative, and anti-convulsant effects. Modifying substitutions at the C5 and C6 positions in furanocoumarins can enhance these activities. CONCLUSION: This study conducted a comprehensive review of all available information on the phytochemical and pharmacological characteristics of Ferulago species. Given the high occurrence of coumarins in this genus, which exhibit potential anti-Alzheimer and anti-microbial properties, it presents promising new therapeutic avenues for addressing these common issues. Further investigation is needed to understand the molecular-level mechanisms of action and to explore their clinical applications.
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BACKGROUND: Breast cancer is one of the most lethal cancers in women. Despite significant advances in the diagnosis and treatment of breast cancer, many patients still succumb to this disease, and thus, novel effective treatments are urgently needed. Natural product coumarin has been broadly investigated since it reveals various biological properties in the medicinal field. Accumulating evidence indicates that histone deacetylase inhibitors (HDACIs) are promising novel anti-breast cancer agents. However, most current HDACIs exhibit only moderate effects against solid tumors and are associated with severe side effects. Thus, to develop more effective HDACIs for breast cancer therapy, hydroxamate of HDACIs was linked to coumarin core, and coumarin-hydroxamate hybrids were designed and synthesized. METHODS: A substituted coumarin moiety was incorporated into the classic hydroxamate HDACIs by the pharmacophore fusion strategy. ZN444B was identified by using the HDACI screening kit and cell viability assay. Molecular docking was performed to explore the binding mode of ZN444B with HDAC1. Western blot, immunofluorescent staining, cell viability, colony formation and cell migration and flow cytometry assays were used to analyze the anti-breast cancer effects of ZN444B in vitro. Orthotopic studies in mouse models were applied for preclinical evaluation of efficacy and toxicity in vivo. Proteomic analysis, dual-luciferase reporter assay, chromatin immunoprecipitation, co-immunoprecipitation, immunofluorescent staining assays along with immunohistochemical (IHC) analysis were used to elucidate the molecular basis of the actions of ZN444B. RESULTS: We synthesized and identified a novel coumarin-hydroxamate conjugate, ZN444B which possesses promising anti-breast cancer activity both in vitro and in vivo. A molecular docking model showed that ZN444B binds to HDAC1 with high affinity. Further mechanistic studies revealed that ZN444B specifically decreases FOS-like antigen 2 (FOSL2) mRNA levels by inhibiting the deacetylase activity of HDAC1 on Sp1 at K703 and abrogates the binding ability of Sp1 to the FOSL2 promoter. Furthermore, FOSL2 expression positively correlates with breast cancer progression and metastasis. Silencing FOSL2 expression decreases the sensitivity of breast cancer cells to ZN444B treatment. In addition, ZN444B shows no systemic toxicity in mice. CONCLUSIONS: Our findings highlight the potential of FOSL2 as a new biomarker and therapeutic target for breast cancer and that targeting the HDAC1-Sp1-FOSL2 signaling axis with ZN444B may be a promising therapeutic strategy for breast cancer.
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Neoplasias de la Mama , Cumarinas , Histona Desacetilasa 1 , Ácidos Hidroxámicos , Transducción de Señal , Cumarinas/química , Cumarinas/farmacología , Humanos , Histona Desacetilasa 1/metabolismo , Histona Desacetilasa 1/antagonistas & inhibidores , Histona Desacetilasa 1/genética , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Neoplasias de la Mama/genética , Animales , Transducción de Señal/efectos de los fármacos , Ácidos Hidroxámicos/farmacología , Ácidos Hidroxámicos/química , Ácidos Hidroxámicos/uso terapéutico , Factor de Transcripción Sp1/metabolismo , Ratones , Inhibidores de Histona Desacetilasas/farmacología , Inhibidores de Histona Desacetilasas/química , Línea Celular Tumoral , Simulación del Acoplamiento Molecular , Proliferación Celular/efectos de los fármacos , Ratones Desnudos , Proteínas Proto-Oncogénicas c-fos/metabolismo , Proteínas Proto-Oncogénicas c-fos/genética , Ratones Endogámicos BALB C , Movimiento Celular/efectos de los fármacos , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/uso terapéutico , Descubrimiento de DrogasRESUMEN
The resin of Ferula sinkiangensis has been traditionally utilized for treating gastrointestinal disorders, inflammation, tumors, various cancers, and alopecia areata. The primary bioactive constituents, sesquiterpene coumarins, have demonstrated notable therapeutic potential against neuroinflammation. In this study, a structure-guided fractionation method was used to isolate nine novel sesquiterpene coumarins from the resin of F. sinkiangensis. These compounds were characterized and structurally elucidated using comprehensive physicochemical and spectroscopic techniques, including calculated electronic circular dichroism (ECD). Anti-neuroinflammatory assays revealed that compounds 2, 3, and 6 significantly inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated BV2 microglial cells, with IC50 values ranging from 1.63 to 12.25 µmol·L-1.
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Antiinflamatorios , Cumarinas , Ferula , Microglía , Óxido Nítrico , Sesquiterpenos , Ferula/química , Cumarinas/farmacología , Cumarinas/aislamiento & purificación , Cumarinas/química , Sesquiterpenos/farmacología , Sesquiterpenos/química , Sesquiterpenos/aislamiento & purificación , Microglía/efectos de los fármacos , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Estructura Molecular , Animales , Ratones , Línea Celular , Lipopolisacáridos/farmacología , Resinas de Plantas/química , Extractos Vegetales/farmacología , Extractos Vegetales/químicaRESUMEN
"Tandem" uncaging systems, in which a photolabile protecting group (PPG) is sensitized by an energy-harvesting antenna, may increase the photosensitivity of PPGs by several orders of magnitude for two-photon (2P) photorelease. Yet, they remain poorly accessible because of arduous multi-step synthesis. In this work, we design efficient tandem uncaging systems by (i) using a convenient assembly of the building blocks relying on click chemistry, (ii) H-bonding induced proximity thus facilitating (iii) photoinduced electron transfer (PeT) as a cooperative mechanism. A strong two-photon absorber electron-donating quadrupolar antenna and various electron-accepting PPGs (mDEAC, MNI or MDNI) were clicked stepwise onto a "tweezer-shaped" pyrido-2,6-dicarboxylate platform whose H-bonding and p-stacking abilities were exploited to keep the antenna and the PPGs in close proximity. The different electron acceptor ability of the PPGs led to dyads with wildly different behaviors. Whilst the MDNI and MNI dyads showed poor dark stability or no photo-uncaging ability due to their too high electron accepting character, the mDEAC dyad benefited from optimum redox potentials to promote PeT and slow down charge recombination, resulting in enhanced uncaging quantum yield (Fu=0.38) compared to mDEAC (Fu=0.014). The unique resulted in large 2P photo-sensitivity in the near-infrared window (240 GM at 710 nm).
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A series of fluorescent carbazole-coumarins exhibiting good photoluminescence quantum yields and thermally activated delayed fluorescence (TADF) properties have been designed and synthetized using computer-aided density functional theory calculations. The TADF characteristics of the carbazole-coumarins were systematically explored both in solution and in the solid state, utilizing poly(methyl methacrylate) (PMMA) as a matrix. The study revealed that the introduction of carbazole units onto the coumarin benzene ring led to compounds with thermally induced reverse intersystem crossing and delayed fluorescence. The study further demonstrated the potential utility of these compounds in practical applications by incorporating them into a Cmr-PMMA-based sensor for molecular oxygen detection. The resulting sensor exhibited promising performance, highlighting the adaptability and efficacy of the synthesized TADF-carbazole-coumarin compounds for reversible molecular oxygen sensing.
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ETHNOPHARMACOLOGICAL RELEVANCE: Plants have been used for a long time in traditional medicine to treat many diseases. The genus Prangos belongs to the Apiaceae family and has various medicinal and aromatic species. Since ancient times, Prangos species have been employed extensively in traditional medicine for different purposes and are especially popular for their aphrodisiac effects. AIM OF THE REVIEW: The goal of this paper is to represent a systematic review of the species in the genus Prangos, including their botanical characteristics, uses in traditional medicine, phytochemical constituents, the composition of the essential oils produced, and the biological properties. MATERIALS AND METHODS: The articles regarding traditional uses and bioactivities of Prangos species were evaluated using electronic databases such as PubMed, Google Scholar, and ScienceDirect. Use of the World Flora Online (WFO) - The Plant List, The International Plant Names Index, the World Checklist of Vascular Plants (2024), and ChemDraw Professional helped complete this compilation. RESULTS: Phytochemical investigations have indicated that coumarins are characteristic constituents of Prangos species, especially prenylated simple coumarins and furanocoumarins, and also flavonoids, terpenoids, and phytosterols occur in this genus. In addition, the essential oils of these plants have been examined. The biological properties of the Prangos species seem worthy of further investigation. Also, some information about the toxicity of these species and their use as ingredients in food products is presented. CONCLUSIONS: This review highlights the evaluation of traditional knowledge, phytochemical profiles, biological activities, and potential uses of Prangos species as foods and spices. Many pharmacological activities have been performed related to their traditional uses, but frequently, the exact mechanism of action remains scientifically unproven. This review has compiled data on the phytochemistry, the active secondary metabolites, the biological properties, and recent advances in Prangos species.
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Apiaceae , Medicina Tradicional , Fitoquímicos , Humanos , Medicina Tradicional/métodos , Apiaceae/química , Fitoquímicos/farmacología , Fitoquímicos/química , Animales , Etnofarmacología , Fitoterapia , Aceites Volátiles/química , Aceites Volátiles/farmacología , Extractos Vegetales/farmacología , Extractos Vegetales/química , Plantas Medicinales/química , Medicina de HierbasRESUMEN
With the increasing resistance of Acinetobacter baumannii (A. baumannii) to antibiotics, researchers have turned their attention to the development of new antimicrobial agents. Among them, coumarin-based heterocycles have attracted much attention due to their unique biological activities, especially in the field of antibacterial infection. In this study, a series of coumarin derivatives were synthesized and screened for their bactericidal activities (Ren et al. 2018; Salehian et al. 2021). The inhibitory activities of these compounds on bacterial strains were evaluated, and the related mechanism of the new compounds was explored. Firstly, the MIC values and bacterial growth curves were measured after compound treatment to evaluate the antibacterial activity in vitro. Then, the in vivo antibacterial activities of the new compounds were assessed on A. baumannii-infected mice by determining the mice survival rates, counting bacterial CFU numbers, measuring inflammatory cytokine levels, and histopathology analysis. In addition, the ROS levels in the bacterial cells were measured with DCFH-DA detection kit. Furthermore, the potential target and detailed mechanism of the new compounds during infection disease therapy were predicted and evidenced with molecular docking. After that, ADMET characteristic prediction was completed, and novel, synthesizable, drug-effective molecules were optimized with reinforcement learning study based on the probed compound as a training template. The interaction between the selected structures and target proteins was further evidenced with molecular docking. This series of innovative studies provides important theoretical and experimental data for the development of new anti-A. baumannii infection drugs.
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Infecciones por Acinetobacter , Acinetobacter baumannii , Antibacterianos , Cumarinas , Ensayos Analíticos de Alto Rendimiento , Pruebas de Sensibilidad Microbiana , Animales , Acinetobacter baumannii/efectos de los fármacos , Cumarinas/farmacología , Cumarinas/química , Cumarinas/uso terapéutico , Ratones , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Antibacterianos/uso terapéutico , Infecciones por Acinetobacter/tratamiento farmacológico , Ensayos Analíticos de Alto Rendimiento/métodos , Simulación del Acoplamiento Molecular , Masculino , Ratones Endogámicos BALB C , FemeninoRESUMEN
BACKGROUND: Powdery mildew, caused by Eeysiphe heraclei, seriously threatens Heracleum moellendorffii Hance. Plant secondary metabolites are essential to many activities and are necessary for defense against biotic stress. In order to clarify the functions of these metabolites in response to the pathogen, our work concentrated on the variations in the accumulation of secondary metabolites in H. moellendorffii during E. heraclei infection. RESULTS: Following E. heraclei infection, a significant upregulation of coumarin metabolites-particularly simple coumarins and associated genes was detected by RNA-seq and UPLC-MS/MS association analysis. Identifying HmF6'H1, a Feruloyl CoA 6'-hydroxylase pivotal in the biosynthesis of the coumarin basic skeleton through ortho-hydroxylation, was a significant outcome. The cytoplasmic HmF6'H1 protein was shown to be able to catalyze the ortho-hydroxylation of p-coumaroyl-CoA and caffeoyl-CoA, resulting in the formation of umbelliferone and esculetin, respectively. Over-expression of the HmF6'H1 gene resulted in increased levels of simple coumarins, inhibiting the biosynthesis of furanocoumarins and pyranocoumarins by suppressing PT gene expression, enhancing H. moellendorffii resistance to powdery mildew. CONCLUSIONS: These results established HmF6'H1 as a resistance gene aiding H. moellendorffii in combatting E. heraclei infection, offering additional evidence of feruloyl-CoA 6'-hydroxylase role in catalyzing various types of simple coumarins. Therefore, this work contributes to our understanding of the function of simple coumarins in plants' defense against powdery mildew infection.
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Ascomicetos , Cumarinas , Metaboloma , Enfermedades de las Plantas , Transcriptoma , Cumarinas/metabolismo , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/genética , Ascomicetos/fisiología , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas , Apiaceae/metabolismo , Apiaceae/genética , Resistencia a la Enfermedad/genéticaRESUMEN
Herein, we describe a visible light-induced C(sp2)-H arylation method for quinoxalin-2(1H)-ones and coumarins using iodonium ylides without the need for external photocatalysts. The protocol demonstrates a broad substrate scope, enabling the arylation of diverse heterocycles through a simple and mild procedure. Furthermore, the photochemical reaction showcases its applicability in the efficient synthesis of biologically active molecules. Computational investigations at the CASPT2//CASSCF/PCM level of theory revealed that the excited state of quinoxalin-2(1H)-one facilitates electron transfer from its π bond to the antibonding orbital of the C-I bond in the iodonium ylide, ultimately leading to the formation of an aryl radical, which subsequently participates in the C-H arylation process. In addition, our calculations reveal that during the single-electron transfer (SET) process, the C-I bond cleavage in iodonium ylide and new C-C bond formation between resultant aryl radical and cationic quinoxaline species take place in a concerned manner. This enables the arylation reaction to efficiently proceed along an energy-efficient route.
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ETHNOPHARMACOLOGICAL RELEVANCE: Ficus erecta, a traditional Chinese She Ethnomedicine, has been historically utilized to treat various inflammatory conditions such as arthritis, nephritis, and osteoporosis. However, the underlying mechanisms accounting for its anti-inflammatory activity, as well as its active components, largely remain elusive. AIM OF THE STUDY: The purpose of this research was to investigate the chemical constituents of F. erecta that contribute to its anti-inflammatory effects. MATERIALS AND METHODS: Coumarins and flavones were obtained from the 95% EtOH extract of F. erecta using virous column chromatography and reversed-phase semipreparative HPLC. The structures of the new compounds were elucidated by extensive analysis of spectroscopic methods, including HRESIMS, 1D and 2D NMR spectra, and CD experiments. Cultured macrophage RAW264.7 cells were utilized for the anti-inflammatory experiments. MTT cell viability assay, Griess reagent method, ELISA, and Western blot experiments were employed to evaluate the anti-inflammatory activity and investigate the related mechanism. RESULTS: Four new (1-4) and eleven previously identified (5-16) coumarins, together with one new (17) and six known flavones (18-23) were isolated from the whole plant of F. erecta. Compounds 7 and 17 significantly reduced nitric oxide (NO) and prostaglandin E2 (PGE2) production without cytotoxic effects. Furthermore, compounds 7 and 17 reduced the production of proinflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 in a concentration-dependent manner. Western blot analysis indicated that compounds 7 and 17 suppressed the expression of iNOS, COX-2, and p-IκBα in LPS-stimulated RAW264.7 macrophage cells. CONCLUSION: The current phytochemical investigations revealed that coumarins and flavones represent the primary chemical constituents of F. erecta. Compounds 7 and 17 exhibit potent anti-inflammatory properties, linked with the inhibition of NF-κB activation by preventing the degradation of IκBα phosphorylation. These compounds may serve as promising candidates for treating or preventing certain inflammatory diseases.
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Antiinflamatorios , Cumarinas , Ficus , Flavonas , Extractos Vegetales , Animales , Ficus/química , Flavonas/farmacología , Flavonas/aislamiento & purificación , Flavonas/química , Cumarinas/farmacología , Cumarinas/aislamiento & purificación , Cumarinas/química , Células RAW 264.7 , Ratones , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Extractos Vegetales/farmacología , Extractos Vegetales/química , Óxido Nítrico/metabolismo , FN-kappa B/metabolismo , Supervivencia Celular/efectos de los fármacos , Macrófagos/efectos de los fármacos , Macrófagos/metabolismoRESUMEN
Aim: This study focused on designing and synthesizing novel derivatives of 3,5,8-trisubstituted coumarin. Results: The synthesized compounds, particularly compound 5, exhibited significant cytotoxic effects on MCF-7 cells, surpassing staurosporine, and reduced toxicity toward MCF-10A cells, highlighting potential pharmacological advantages. Further, compound 5 altered the cell cycle and significantly increased apoptosis in MCF-7 cells, involving both early (41.7-fold) and late stages (33-fold), while moderately affecting necrotic signaling. The antitumor activity was linked to a notable reduction (4.78-fold) in topoisomerase IIß expression. Molecular modeling indicated compound 5's strong affinity for EGFR, human EGF2 and topoisomerase II proteins. Conclusion: These findings highlight compound 5 as a multifaceted antitumor agent for breast cancer.
[Box: see text].
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Antineoplásicos , Apoptosis , Neoplasias de la Mama , Proliferación Celular , Cumarinas , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Cumarinas/química , Cumarinas/farmacología , Cumarinas/síntesis química , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Proliferación Celular/efectos de los fármacos , Femenino , Apoptosis/efectos de los fármacos , ADN-Topoisomerasas de Tipo II/metabolismo , Relación Estructura-Actividad , Células MCF-7 , Estructura Molecular , Línea Celular Tumoral , Ciclo Celular/efectos de los fármacos , Receptores ErbB/metabolismo , Receptores ErbB/antagonistas & inhibidoresRESUMEN
Coumarins are secondary metabolites made up of benzene and α-pyrone rings fused together that can potentially treat various ailments, including cancer, metabolic, and degenerative disorders. Coumarins are a diverse category of both naturally occurring as well as synthesized compounds with numerous biological and therapeutic properties. Coumarins as fluorophores play a key role in fluorescent labeling of biomolecules, metal ion detection, microenvironment polarity detection, and pH detection. This review provides a detailed insight into the characteristics of coumarins as well as their biosynthesis in plants and metabolic pathways. Various synthetic strategies for coumarin core involving both conventional and green methods have been discussed comparing advantages and disadvantages of each method. Conventional methods discussed are Pechmann, Knoevenagel, Perkin, Wittig, Kostanecki, Buchwald-Hartwig, and metal-induced coupling reactions such as Heck and Suzuki, as well as green approaches involving microwave or ultrasound energy. Various pharmacological applications of coumarin derivatives are discussed in detail. The structural features and conditions responsible for influencing the fluorescence of coumarin core are also elaborated.
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Cumarinas , Colorantes Fluorescentes , Cumarinas/química , Cumarinas/síntesis química , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Humanos , Estructura Molecular , Productos Biológicos/química , Productos Biológicos/síntesis químicaRESUMEN
Research on nanoparticles (NPs) and future elevated CO2 (eCO2) is extensive, but the effects of SeNPs on plant growth and secondary metabolism under eCO2 remain uncertain. In this study, we explored the impact of SeNPs and/or eCO2 on the growth, physiology, chemical composition (primary metabolites, coumarins, and essential oils), and antioxidant capacity of Trachyspermum (T.) ammi. The treatment with SeNPs notably improved the biomass and photosynthesis of T. ammi plants, particularly under eCO2 conditions. Plant fresh and dry weights were improved by about 19, 33 and 36% in groups treated by SeNPs, eCO2, and SeNPs + eCO2, respectively. SeNPs + eCO2 induced photosynthesis, consequently enhancing sugar and amino acid levels. Similar to the increase in total sugars, amino acids showed variable enhancements ranging from 6 to 42% upon treatment with SeNPs + eCO2. At the level of the secondary metabolites, SeNPs + eCO2 substantially augmented coumarin biosynthesis and essential oil accumulation. Consistently, there were increases in coumarins and essential oil precursors (shikimic and cinnamic acids) and their biosynthetic enzymes. The enhanced accumulation of coumarins and essential oils resulted in increased overall antioxidant activity, as evidenced by improvements in FRAP, ORAC, TBARS, conjugated dienes, and inhibition % of hemolysis. Conclusively, the application of SeNPs demonstrates significant enhancements in plant growth and metabolism under future CO2 conditions, notably concerning coumarin metabolism and essential oil production of T. ammi.
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Dióxido de Carbono , Cumarinas , Aceites Volátiles , Selenio , Aceites Volátiles/metabolismo , Cumarinas/metabolismo , Dióxido de Carbono/metabolismo , Dióxido de Carbono/farmacología , Selenio/metabolismo , Selenio/farmacología , Antioxidantes/metabolismo , Nanopartículas , Fotosíntesis/efectos de los fármacosRESUMEN
A total of 37 characteristic terpenylated coumarins (1-25), including 17 undescribed compounds (1-5, 6a/6b, 7-10, 11a/11b-13a/13b), have been isolated from the root of Ferula ferulaeoides. Meanwhile, twelve pairs of enantiomers (6a/6b, 11a/11b-15a/15b, 17a/17b, 18a/18b, 20a/20b-22a/22b, and 25a/25b) were chirally purified. The structures of these new compounds were elucidated using HRESIMS, UV, NMR, and calculated 13C NMR with a custom DP4 + analysis. The absolute configurations of all the compounds were determined for the first time using electronic circular dichroism (ECD). Then, their inhibitory effects on nitric oxide (NO) production were evaluated with LPS-induced BV-2 microglia. Compared with the positive control minocycline (IC50 = 59.3 µM), ferulaferone B (2) exhibited stronger inhibitory potency with an IC50 value of 12.4 µM. The immunofluorescence investigation indicated that ferulaferone B (2) could inhibit Iba-1 expression in LPS-stimulated BV-2 microglia.
Asunto(s)
Cumarinas , Relación Dosis-Respuesta a Droga , Ferula , Lipopolisacáridos , Microglía , Óxido Nítrico , Cumarinas/farmacología , Cumarinas/química , Cumarinas/aislamiento & purificación , Ferula/química , Microglía/efectos de los fármacos , Microglía/metabolismo , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/biosíntesis , Óxido Nítrico/metabolismo , Animales , Estructura Molecular , Ratones , Relación Estructura-Actividad , Lipopolisacáridos/farmacología , Lipopolisacáridos/antagonistas & inhibidores , Raíces de Plantas/químicaRESUMEN
PURPOSE: Toxoplasmosis is caused by the parasite Toxoplasma gondii (T. gondii). In immunocompetent individuals, the infection is often asymptomatic; however, in expectant mothers and those with immune system deficiencies, complications may arise. Consequently, there is a need for new drugs that cause minimal damage to host cells. The purpose of this study was to investigate the in vitro antiparasitic efficacy of quinolone-coumarin hybrids QC1-QC12, derived from quinolone antibacterials and novobiocin, against T. gondii. METHODS: The derivatives were compared with novobiocin and ciprofloxacin during testing, with pyrimethamine used as a positive control. We conducted the MTT assay to examine the anti-toxoplasmic effects of the test compounds and novobiocin. Evaluation included the infection and proliferation indices, as well as the size and number of plaques, based on the viability of both healthy and infected cells. RESULTS: The in vitro assays revealed that QC1, QC3, QC6, and novobiocin, with selectivity indices (SIs) of 7.27, 13.43, and 8.23, respectively, had the least toxic effect on healthy cells and the highest effect on infected cells compared to pyrimethamine (SI = 3.05). Compared to pyrimethamine, QC1, QC3, QC6, and novobiocin Without having a significant effect on cell viability, demonstrated a significant effect on reducing in both infection index and proliferation index, in addition to reducing the quantity and dimensions of plaques ( P < 0.05). CONCLUSION: Based on our results, QC1, QC3, QC6, and novobiocin due to their significant therapeutic effects could be considered as potential new leads in the development of novel anti-Toxoplasma agents.
Asunto(s)
Novobiocina , Quinolonas , Toxoplasma , Toxoplasma/efectos de los fármacos , Novobiocina/farmacología , Animales , Quinolonas/farmacología , Quinolonas/química , Fluoroquinolonas/farmacología , Cumarinas/farmacología , Cumarinas/química , Antiprotozoarios/farmacología , Humanos , Supervivencia Celular/efectos de los fármacos , Pruebas de Sensibilidad ParasitariaRESUMEN
Phytochemical profiling followed by antimicrobial and anthelmintic activity evaluation of the Australian plant Geijera parviflora, known for its customary use in Indigenous Australian ceremonies and bush medicine, was performed. In the present study, seven previously reported compounds were isolated including auraptene, 6'-dehydromarmin, geiparvarin, marmin acetonide, flindersine, and two flindersine derivatives from the bark and leaves, together with a new compound, chlorogeiparvarin, formed as an artefact during the isolation procedure and isolated as a mixture with geiparvarin. Chemical profiling allowed for a qualitative and quantitative comparison of the compounds in the leaves, bark, flowers, and fruit of this plant. Subsequently, a subset of these compounds as well as crude extracts from the plant were evaluated for their antimicrobial and anthelmintic activities. Anthelmintic activity assays showed that two of the isolated compounds, auraptene and flindersine, as well as the dichloromethane and methanol crude extracts of G. parviflora, displayed significant activity against a parasitic nematode (Haemonchus contortus). This is the first report of the anthelmintic activity associated with these compounds and indicates the importance of such fundamental explorations for the discovery of bioactive phytochemicals for therapeutic application(s).
RESUMEN
Heracleum mantegazzianum is an invasive species in middle Europe. The mode of action of its invasiveness is still not known. Our study focuses on observation of potential allelopathic influence by the production and release of phytochemicals into its environment. Plant material was collected four times within one season (April, May, June, July 2019) at locality Lekárovce (eastern Slovakia) for comparison of differences in composition and potential allelopathy. Water extracts from collected samples were used for different biological assays. The total phenols and flavonoids were determined spectrophotometrically. The profile and content of phenolic components, including coumarins, were determined by two techniques of liquid chromatography along with in vitro evaluation of the free radical scavenging activity of extracts (DPPH, Hydroxyl, Superoxide, and FRAP). The changes in composition in extracts in different seasonal periods were evident as well as potential phytotoxic activity in some concentrations on specific model plants. The slight antioxidant activity was noted. The invasiveness of the current species could be supported by the excretion of its phytochemicals into its surroundings and by different modes of action influencing living organisms in its environment.
RESUMEN
The post-column reaction method enables the evaluation of the antiradical capacity of individual components in a mixture by separating the components using HPLC and measuring stable free radical (e.g., DPPHâ) scavenging that occurs after the chromatography column. The equipment typically consists of two detectors. The first records signals of the analytes leaving the column. The second records radical scavenging by the analytes, which appears as a negative band. The recorded signals are found on two separate chromatograms, which must be combined to interpret the results. In this study, a single DAD detector was used behind the post-column reactor, enabling the simultaneous recording of the analyte bands and negative signals, indicating radical scavenging. The objective of this study was to evaluate the antiradical capacity of key compounds found in two herbal raw materials used in traditional Chinese medicine. Saposhnikovia divaricata roots contain phenolic acids, chromones, and furanocoumarins. Chlorogenic acid, rosmarinic acid, and imperatorin demonstrated strong radical scavenging, while prim-O-glucoslocimifugin showed a weaker response, both in standards and in root extracts. However, scavenging was not observed for cimifugin and 4'-O-ß-D-glucosyl-5-O-methylvisamminol. Astragalus mongholicus roots contain astragalosides I-IV (triterpene saponins). None of these showed DPPHâ scavenging. Furthermore, additional signals were observed, indicating the presence of unidentified radical scavenging compounds.