Coumarin Type Research Articles

Combined metabolome and transcriptome reveal HmF6’H1 regulating simple coumarin accumulation against powdery mildew infection in Heracleum moellendorffii Hance

BackgroundPowdery 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.ResultsFollowing 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.ConclusionsThese 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.

The chromosome-scale assembly of the Notopterygium incisum genome provides insight into the structural diversity of coumarins

Coumarins, derived from the phenylpropanoid pathway, represent one of the primary metabolites found in angiosperms. The alignment of the tetrahydropyran (THP) and tetrahydrofuran (THF) rings with the lactone structure results in the formation of at least four types of complex coumarins. However, the mechanisms underlying the structural diversity of coumarin remain poorly understood. Here, we report the chromosome-level genome assembly of Notopterygium incisum, spanning 1.64 Gb, with a contig N50 value of 22.7 Mb and 60,021 annotated protein-coding genes. Additionally, we identified the key enzymes responsible for shaping the structural diversity of coumarins, including two p-coumaroyl CoA 2′-hydroxylases crucial for simple coumarins basic skeleton architecture, two UbiA prenyltransferases responsible for angular or linear coumarins biosynthesis, and five CYP736 cyclases involved in THP and THF ring formation. Notably, two bifunctional enzymes capable of catalyzing both demethylsuberosin and osthenol were identified for the first time. Evolutionary analysis implies that tandem and ectopic duplications of the CYP736 subfamily, specifically arising in the Apiaceae, contributed to the structural diversity of coumarins in N. incisum. Conclusively, this study proposes a parallel evolution scenario for the complex coumarin biosynthetic pathway among different angiosperms and provides essential synthetic biology elements for the heterologous industrial production of coumarins.

Metabolomic Profiling Reveals the Quality Variations in Citri Reticulatae Pericarpium (Citrus reticulata Blanco cv. Chachiensis) with Different Storage Ages in Response to "Candidatus Liberibacter Asiaticus" Infection.

Citri Reticulatae Pericarpium, especially the pericarp of Citrus reticulata Blanco cv. Chachiensis (PCRC), is an important edible and medicinal ingredient for health and pharmacological properties. Citrus Huanglongbing, a devastating disease that currently threatens the citrus industry worldwide, is caused by a phloem-limited alpha-proteobacterium, "Candidatus Liberibacter asiaticus" (CLas). The industry of cultivar Chachiensis has been suffering from HLB. Although HLB affected the quality of citrus fruit, whether the quality of PCRC was affected by HLB remains unclear. In this study, we compared the metabolite profiles between HLB-affected and healthy PCRC from three sources: fresh, 6-month-old, and 9-year-old PCRC, through the untargeted LC-MS method. Compared to healthy controls, various types of bioactive compounds, mainly flavonoids, terpenoids, alkaloids, coumarins, polysaccharides, and phenolic acids, accumulated in HLB-affected PCRC, especially in the HLB-affected 9-year PCRC. In particular, isorhamnetin, isoliquiritigenin, luteolin 7-O-beta-D-glucoside, limonin, geniposide, pyrimidodiazepine, scoparone, chitobiose, m-coumaric acid, malonate, and pantothenic acid, which contributed to the pharmacological activity and health care effects of PCRC, were highly accumulated in HLB-affected 9-year-old PCRC compared to the healthy control. Multibioassay analyses revealed that HLB-affected 9-year-old PCRC had a higher content of total flavonoids and total polyphenols and exhibited similar antioxidant capacity as compared to healthy controls. The results of this study provided detailed information on the quality of HLB-affected PCRC.

Anabolic metabolism of autotoxic substance coumarins in plants

Background Autotoxicity is an intraspecific manifestation of allelopathy in plant species. The specialized metabolites and their derivatives that cause intraspecific allelopathic inhibition in the plant are known as autotoxic substances. Consequently, autotoxic substances production seriously affects the renewal and stability of ecological communities. Methods This article systematically summarizes the types of autotoxic substances present in different plants. They mainly include phenolic compounds, terpenoids, and nitrogenous organic compounds. Phenolic coumarins are the main autotoxic substances in many plants. Therefore, we also discuss differences in coumarin types and content among plant varieties, developmental stages, and tissue parts, as well as their mechanisms of autotoxicity. In addition, we review the metabolic pathways involved in coumarin biosynthesis, the key enzymes, genes, and transcription factors, as well as factors affecting coumarin biosynthesis. Results Coumarin biosynthesis involves three stages: (1) the formation of the coumarin nucleus; (2) acylation, hydroxylation, and cyclization; (3) structural modification. The key enzymes involved in the coumarin nuclear formation stage include PAL, C4H, 4CL, HCT, CAOMT, COSY, F6’H, and CCoAOMT1, and the key genes involved include BGA, CYP450 and MDR, among others. Ortho-hydroxylation is a key step in coumarin biosynthesis and PS, COSY and S8H are the key enzymes involved in this process. Finally, UGTs are responsible for the glycosylation modification of coumarins, and the MaUGT gene may therefore be involved in coumarin biosynthesis. Conclusion It is important to elucidate the autotoxicity and anabolic mechanisms of coumarins to create new germplasms that produce fewer autotoxic substances.

Network pharmacology and molecular docking reveal potential mechanism of esculetin in the treatment of ulcerative colitis.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease of the colonic mucosa. Esculetin is a type of natural coumarin that has many pharmacological activities such as antioxidant, anticancer, anti-inflammatory, etc. A previous study showed that esculetin improved intestinal inflammation and reduced serum proinflammatory cytokines in UC. The present study aimed to utilize network pharmacology and molecular docking to explore the potential mechanism of esculetin against UC. The potential gene targets of esculetin were predicted through SwissTargetPrediction and Super-PRED web servers. UC-related genes were obtained from DisGeNet, OMIM, and GeneCards databases. The overlap between gene targets of esculetin and UC-related genes were identified as the potential targets of esculetin against UC. The interaction between these overlapping genes was analyzed by the STRING database and the core genes were identified by Cytoscape platform. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of the core genes were then performed. And the results of these analyses were further confirmed through molecular docking. A total of 50 overlapping genes were identified as the potential action targets of esculetin against UC. Among them, 10 genes (AKT1, STAT1, CCND1, SRC, PTGS2, EGFR, NFKB1, ESR1, MMP9, SERPINE1) were finally identified as the core genes. The Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis results showed that the top signaling pathway associated with the core genes of esculetin against UC was the prolactin (PRL) signaling pathway. Molecular docking results showed that esculetin has a strong binding affinity to the core genes, as well as PRL and prolactin receptor. This study suggests that esculetin may have a crucial impact on UC through the PRL signaling pathway and provides insights into the potential mechanism of esculetin in the treatment of UC, which may shed light on the mechanism and treatment of UC.

Aloe Vera Extract Gel-Biosynthesized Selenium Nanoparticles Enhance Disease Resistance in Lettuce by Modulating the Metabolite Profile and Bacterial Endophytes Composition.

The use of nanotechnology to suppress crop diseases has attracted significant attention in agriculture. The present study investigated the antifungal mechanism by which aloe vera extract gel-biosynthesized (AVGE) selenium nanoparticles (Se NPs) suppressed Fusarium-induced wilt disease in lettuce (Lactuca sativa). AVGE Se NPs were synthesized by utilizing sodium selenite as a Se source and AVGE as a biocompatible capping and reducing agent. Over 21 d, 2.75% of total AVGE Se NPs was dissolved into Se ions, which was more than 8-fold greater than that of bare Se NPs (0.34%). Upon exposure to soil applied AVGE Se NPs at 50 mg/kg, fresh shoot biomass was significantly increased by 61.6 and 27.8% over the infected control and bare Se NPs, respectively. As compared to the infected control, the shoot levels of citrate, isocitrate, succinate, malate, and 2-oxo-glutarate were significantly upregulated by 0.5-3-fold as affected by both Se NPs. In addition, AVGE Se NPs significantly increased the shoot level of khelmarin D, a type of coumarin, by 4.40- and 0.71-fold over infected controls and bare Se NPs, respectively. Additionally, AVGE Se NPs showed greater upregulation of jasmonic acid and downregulation of abscisic acid content relative to bare Se NPs in diseased shoots. Moreover, the diversity of bacterial endophytes was significantly increased by AVGE Se NPs, with the values of Shannon index 40.2 and 9.16% greater over the infected control and bare Se NPs. Collectively, these findings highlight the significant potential of AVGE Se NPs as an effective and biocompatible strategy for nanoenabled sustainable crop protection.

Protective effects of Angelica decursiva Franchet & Savatier on allergic responses through enhancement of Nrf2 and suppression of NF-kB/MMP-9 in ovalbumin-exposed mice

Ethnopharmacological relevanceAngelica decursiva Franchet & Savatier is a traditional medicinal plant used to treat asthma, cough, headache, pyrexia and thick phlegm in China, Japan and Korea. A. decursiva contains many types of coumarins, which can exert several pharmacological activities including anti-inflammatory and antioxidant properties for treating various diseases such as pneumonitis, atopic dermatitis, diabetes, and Alzheimer's disease. Aim of the studyIn this study, we analyzed the components of A. decursiva ethanol extract (ADE) by high performance liquid chromatography (HPLC) and investigated the therapeutic effects of ADE against allergic asthma using lipopolysaccharide (LPS) stimulated RAW264.7 cells and an ovalbumin (OVA)-exposed allergic asthma model. To elucidate the mechanism of action of ADE, we examined the protein expression through network pharmacological analysis. Materials and methodsTo establish asthma model, the mice were sensitized on day 0 and 14 via intraperitoneal injection of OVA with aluminum hydroxide. The mice were inhaled with OVA using an ultrasonic nebulizer on day 21, 22 and 23. ADE (50 and 100 mg/kg) was administered to mice by oral gave form day 18–23. On day 24, airway hyperresponsiveness (AHR) was measured using flexivent. On day 25, the mice were sacrificed and collected bronchoalveolar lavage fluids (BALF), serum and lung tissue. In LPS-stimulated RAW264.7 cell, nitric oxide and cytokines were measured. Additionally, expression of nuclear factor erythroid-2-related factor (Nrf2) and suppression of nuclear factor (NF)-κB were detected using double-immunofluorescence. ResultsWe detected the five coumarin components which included nodakenin, umbelliferon, (−)-marmesin (=nodakenetin), bergapten, and decursin, in ADE by high performance liquid chromatography. Treatment with ADE decreased the production of nitric oxide, interleukin (IL)-6 and tumor necrosis factor (TNF)-α in LPS-stimulated RAW264.7 cells accompanied by the enhanced expression of nuclear factor erythroid-2-related factor (Nrf2) and suppression of nuclear factor (NF)-κB. In the asthma model, the administration of ADE reduced inflammatory cell count and airway hyperresponsiveness in OVA-exposed animals with decreased levels of IL-4, IL-13, and OVA-specific immunoglobulin E. These results were accompanied by the reduction of pulmonary inflammation and mucus secretion. Furthermore, ADE administration inhibited the expression of NF-κB and matrix metalloproteinase (MMP)-9 in OVA-exposed animals, which was consistent with the results of network pharmacological analysis. ConclusionThis study demonstrated that ADE effectively attenuated allergic inflammation induced by OVA inhalation through the enhancement of Nrf2 expression and suppression of NF-κB expression. Therefore, ADE may be a potential therapeutic agent for controlling asthma.

Coumarins of genus Ferula L. (Apiaceae Lindl.)

The biologically active coumarins from Ferula L. species of the family Apiaceae Lindl. for the period 1970 to 2022 have been reviewed. The phytochemical investigation of different parts of Ferula L., including gum resin, leaves, fruits, seeds, roots, rhizomes, and resins led to the separation of different types of coumarins. Nearly 185 coumarins were isolated from 35 species of Ferula L. growing in different countries. Coumarins are represented mainly by umbelliferone (7-O-hydroxycoumarin) derivatives substituted in the C-7 position of aglycone, furanocoumarins and metabolites have terpene fragments, esters and glycosides. Umbelliferon is found as a taxon for the genus Ferula L. Some «unusual» metabolites have a furan fragment attached to the pyrone ring. Coumarins are of the psoralen type, containing a furan ring in the C-6 and C-7 positions of the primary skeleton. The rare coumarins with terpene fragments (hemiterpene, monoterpen, sesquiterpene) were reported. The biological activities of some extracts and individual metabolites such as antiinflammatory, cytotoxicity, antibacterial, antileishmanial, antiviral, antigenotoxic, antitumor, anticoagulant, antioxidant, antimycobacterial, inhibition a-glucosidase, antileishmanial were found.

Suberosin Alleviates Sepsis-Induced Lung Injury in A Rat Model of Cecal Ligation and Puncture

Background/aims Sepsis is one of the major problems encountered in intensive care units, causing organ damage and increasing mortality. Suberosin (SBR) is a type of coumarin with antioxidant and anti-inflammatory activities. The goal of this study is to explore the protective effects of SBR on the lungs in a rat model of sepsis. Methods Male Wistar rats were utilized in this study. A cecal ligation and puncture (CLP) model was applied to induce sepsis. Rats were separated into six groups with nine animals in each group, including healthy control, SBR, CLP, and CLP + SBR (5, 10, and 20 mg/kg) groups. Superoxide dismutase (SOD), glutathione (GSH) enzyme activities, and malondialdehyde (MDA) level were measured via enzyme-linked immunosorbent assay (ELISA). The messenger RNA (mRNA) expressions of tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) were evaluated by real-time polymerase chain reaction (RT-PCR). Histopathological changes in the lungs were investigated with hematoxylin and eosin (H&E). Results MDA levels and GSH and SOD enzyme activities were negatively affected in the CLP group, but SBR treatment ameliorated these oxidative stress parameters in the SBR1-3 groups (p< 0.05). The mRNA expressions of TNF-α and IL-1β were increased in the CLP group, and SBR treatment decreased those expression levels in a dose-dependent manner (p < 0.05). Organ damage and necrosis were seen in the CLP group and were alleviated in the SBR3 group. Immunohistochemical (IHC) analysis of lung tissues demonstrated decreased TNF-α and IL-1β immunopositivity in the SBR1-3 groups (p< 0.05). Conclusions SBR ameliorated sepsis-related lung injury in a dose-dependent manner. This compound has significant potential as a future agent in the treatment of sepsis.

Mechanistic Insights into the Ameliorative Effect of Cichoriin on Diabetic Rats-Assisted with an In Silico Approach.

Rats were allocated into five groups. Group I was considered as the control group, while the other groups were HFD/STZ-induced diabetic rats. Group II was assigned as the diabetic control. Groups III and IV were treated with cichoriin (50 or 100 mg/kg, respectively). Group V received glibenclamide (5 mg/kg) (as a positive control). The blood glucose (BG), serum insulin, triglycerides (TG), total cholesterol (TC), total antioxidant capacity (TAC), catalase, hepatic superoxide dismutase (SOD) and content of malondialdehyde (MDA) were assessed. Histopathological and immunohistochemistry analysis of pancreatic tissue were performed. mRNA and protein expressions of GLUT4, AMPK, and PI3K were estimated. Cichoriin treatment ameliorated HFD/STZ-induced diabetic conditions and mitigated the histopathological characteristics of the pancreas, as well as increasing pancreatic insulin expression. This decreased the levels of BG, TG, TC, and MDA and improved the TAC, catalase and SOD contents. Cichoriin demonstrated upregulation of mRNA and protein expressions of GLUT4, AMPK, and PI3K. The in silico binding of cichoriin with GLUT4, AMPK, and PI3K supported the possible current activities. Collectively, this work highlighted the potential role of cichoriin in mitigating HFD/STZ-induced diabetic conditions and showed it to be a valuable product.

Rapid characterization of the chemical constituents of Wangbi Capsule by UPLC coupled with Fourier transform ion cyclotron resonance mass spectrometry

Wangbi Capsule is a compound preparation composed of 17 traditional Chinese medicines, which is widely used in the treatment of rheumatoid arthritis. In our study, a rapid and straightforward analytical method was successfully established by using Ultra performance liquid chromatography coupled with Fourier transform ion cyclotron resonance mass spectrometry technology to quickly separate and identify the chemical constituents of Wangbi Capsule. The chromatography was performed on a Universal XB-C18 column (2.1 mm × 150 mm, 3 μm) by the mobile phase containing acetonitrile (A)-0.1% formic acid and water (B) at the flow rate of 0.2 mL/min. The positive and negative ions of the samples were analyzed by extraction ion chromatography. Based on accurate mass spectrometry informations such as excimer ions and fragment ions, combined with the reference materials and the reference literature, 140 compounds in the Wangbi Capsule were identified or preliminarily characterized. The results of the study show that Wangbi Capsules mainly contain 3 types of nucleosides, 31 types of alkaloids, 12 types of organic acids, 29 types of flavonoids, 12 types of monoterpene glycosides, 30 types of coumarins, 10 types of chromones, 3 types of saponins, 6 kinds of phenylethanoid glycosides and other chemical components. The method established in this study can quickly and efficiently identify the chemical constituents in Wangbi Capsules. It is hoped that it will have a certain significance for the characterization of other Chinese medicine components and lay the foundation for pharmacological research and subsequent in vivo studies of Wangbi Capsules.

A Semi-Vectorial Morphological Segmentation Multi-Component Images of Coumarins on Thin Layer Combined with Laser for Better Separation

In this work, we propose an approach for the separation of coumarins from thin-layer morphological segmentation based on the acquisition of multicomponent images integrating different types of coumarins. The first step is to make a segmentation by region, by thresholding, by contour, etc. of each component of the digital image. Then, we proceeded to the calculations of parameters of the regions such as the color standard deviation, the color entropy, the average color of the pixels, the eccentricity from an algorithm on the matlab software. The mean color values atR = 91.20 in red, atB = 213.21 in blue showed the presence of samidin in the extract. The color entropy values HG = 5.25 in green and HB = 4.04 in blue also show the presence of visnadine in the leaves of Desmodium adscendens. These values are used to consolidate the database of separation and discrimination of the types of coumarins. The relevance of our coumarin separation or coumarin recognition method has been highlighted compared to other methods, such as the one based on the calculation of frontal ratios which cannot discriminate between two coumarins having the same frontal ratio. The robustness of our method is proven with respect to the separation and identification of some coumarins, in particular samidin and anglicine.

Cyclometalated iridium-coumarin ratiometric oxygen sensors: improved signal resolution and tunable dynamic ranges.

In this work we introduce a new series of ratiometric oxygen sensors based on phosphorescent cyclometalated iridium centers partnered with organic coumarin fluorophores. Three different cyclometalating ligands and two different pyridyl-containing coumarin types were used to prepare six target complexes with tunable excited-state energies. Three of the complexes display dual emission, with fluorescence arising from the coumarin ligand, and phosphorescence from either the cyclometalated iridium center or the coumarin. These dual-emitting complexes function as ratiometric oxygen sensors, with the phosphorescence quenched under O2 while fluorescence is unaffected. The use of blue-fluorescent coumarins results in good signal resolution between fluorescence and phosphorescence. Moreover, the sensitivity and dynamic range, measured with Stern–Volmer analysis, can be tuned two orders of magnitude by virtue of our ability to synthetically control the triplet excited-state ordering. The complex with cyclometalated iridium 3MLCT phosphorescence operates under hyperoxic conditions, whereas the two complexes with coumarin-centered phosphorescence are sensitive to very low levels of O2 and function as hypoxic sensors.

Excited State Proton Transfers in Hybrid Compound Based on Indoline Spiropyran of the Coumarin Type and Azomethinocoumarin in the Presence of Metal Ions.

Spectral-luminescence properties of a hybrid compound containing a coumarin-type spiropyran and an azomethinocoumarin fragment in toluene-acetonitrile solution in the presence of Li+, Ca2+, Zn2+ and Mg2+ ions are reported. Two excited state proton transfers can occur in the hybrid compound—the transfer of a proton from the OH group of the 7-hydroxy coumarin tautomer to the N atom of the C=N bond of the azomethine fragment leading to green ESIPT fluorescence with a maximum at 540 nm and from the OH group of the 7-hydroxy coumarin tautomer to the carbonyl group of the pyrone chromophore, which leads to the formation of the 2-hydroxyl-tautomer T of coumarin with blue fluorescence with a maximum at 475 nm. Dependence of these excited state proton transfers on the metal nature and irradiation with an external UV source is discussed.

Advances in the Extraction, Purification, Structural Characteristics and Biological Activities of Eleutherococcus senticosus Polysaccharides: A Promising Medicinal and Edible Resource With Development Value.

In recent years, natural polysaccharides have received growing attention and interest in view of their values in food, medical, cosmetics and other fields. Eleutherococcus senticosus (E. senticosus) is a medicine and food homologous plant that possess anti-tumor, anti-inflammatory, central nervous system and cardiovascular protection, anti-radiation, enhancement of human microcirculation, improvement of physical fatigue effects, mainly based on lignans, flavonoids and coumarin types. E. senticosus polysaccharides (ESPS), act as a kind of polysaccharide extracted and isolated from the root and rhizome of E. senticosus, have been found in many applications of medicine and food for their unique biological activity. Nevertheless, the existing studies are mostly concerned with small molecules of E. senticosus, less attention is paid to polysaccharides. Moreover, the types and structural characterization of ESPS reported in existing literature were also not summarized. In this paper, the research progress of ESPS is reviewed from the aspects of extraction, separation, structural characterization and biological activity, future perspectives from points of efficient extraction, resource utilization and quality control standards were also proposed, which provide reference for the further development and utilization of ESPS.

Comparative Antiseizure Analysis of Diverse Natural Coumarin Derivatives in Zebrafish.

Coumarins are a well-known group of plant secondary metabolites with various pharmacological activities, including antiseizure activity. In the search for new antiseizure drugs (ASDs) to treat epilepsy, it is yet unclear which types of coumarins are particularly interesting as a systematic analysis has not been reported. The current study performed behavioral antiseizure activity screening of 18 different coumarin derivatives in the larval zebrafish pentylenetetrazole (PTZ) model using locomotor measurements. Activity was confirmed for seven compounds, which lowered seizure-like behavior as follows: oxypeucedanin 38%, oxypeucedanin hydrate 74%, notopterol 54%, nodakenetin 29%, hyuganin C 35%, daphnoretin 65%, and pimpinellin 60%. These coumarins, together with nodakenin, underwent further antiepileptiform analysis by local field potential recordings from the zebrafish opticum tectum (midbrain). All of them, except for nodakenetin, showed pronounced antiepileptiform activity, decreasing PTZ-induced elevation in power spectral density (PSD) by 83–89% for oxypeucedanin, oxypeucedanin hydrate, and notopterol, 77% for nodakenin, 26% for nodakenetin, 65% for hyuganin C, 88% for daphnoretin, and 81% for pimpinellin. These data demonstrate the potential of diverse coumarin scaffolds for ASD discovery. Finally, the structural differences between active and inactive coumarins were investigated in silico for oxypeucedanin hydrate and byacangelicin for their interaction with GABA-transaminase, a hypothetical target.

Endophytic Fungi Penicillium species BCt Phytochemicals Inhibit Replication of Enzymes of Human Immuno-deficiency Virus 1 in in vitro and in silico Studies

&#x0D; The present investigation was aimed to know the coumarins in the methanol extract of endophytic fungi, Penicillium species BCt isolated from Calophyllum tomentosum bark tissues using qualitative and GC-MS analysis. The endophytic extract was evaluated for anti-HIV activity on three replicating enzymes in vitro and in silico. The methanol extract of Penicillium species confirmed the presence of coumarins in four qualitative methods and yielded four different types of coumarins in GC-MS. In GC-MS analysis, totally seven different phytochemicals were identified based on retention time and compared with available library data. The four coumarins are coumarin (2H-1-benzopyran-2-one), coumaric acid (3-benzofuran-carboxylic acid), hynecromone (coumarin 4), 4-hydroxy-9-(3-methyl-2-butyl) furo (3,2-g) chloronen-7-one) and other three are common phytochemicals. The HIV-1 RT (98) was strongly inhibited by the endophytic fungal extract compared to integrase (118) and protease (158) in vitro analysis. Highest inhibition of integrase was observed with coumarilic acid (-17.62) when attached to Glu-35, Asn-38, Ser-39 amino acids. The protease was inhibited strongly by hymecromone (-16.39) when attached to amino acids of Val-77, Glu-34, Pro-79, Gly-78. The inhibition of RT was observed with coumarilic acid by attaching to Ala-445, Arg-567, Asp-456, Glu-478, Ser-499, Asn-474 (-23.54) significantly. Based on above results, the endophytic fungal coumarins have the ability to inhibit the three replicating enzymes of HIV-1 significantly. The in-silico results are evidence for how coumarins inhibiting the HIV replicating proteins by binding at specific amino acids. The results will help to understand how and where phytochemicals bind to target proteins to inhibit their action and it may help to identification of drugs to treat HIV. To validate our results, the in vivo research is needed.

Rapid characterization of the chemical constituents of Duzhong Jiangya tablet by HPLC coupled with Fourier transform ion cyclotron resonance mass spectrometry.

Duzhong Jiangya tablet is a hypotensive drug. In this study, high-performance liquid chromatography-Fourier transform-ion cyclotron resonance-mass spectrometry technology was used to quickly identify its chemical composition. SinoChrom ODS-BP column (250mm × 4.6mm, 5 μm) was used. The mobile phase was acetonitrile(A)-0.1% formic acid solution(B). The flow rate was 1mL/min. Extracted ion chromatogram was used to analyze the samples in positive and negative ion modes. Based on the accurate mass spectrometry information (such as quasi-molecular ions and fragment ions) obtained from the instrument, combined with reference compounds and literature, the chemical composition of Duzhong Jiangya Tablets was identified. A total of 131 compounds were identified, including four types of penylpropanoids, six types of phenylethanoid glycosides, 10 types of organic acids, 14 types of iridoids, 12 types of lignans, 18 types of alkaloids, seven types of coumarins, and 60 kinds of flavonoids. This established method can quickly and efficiently identify chemical constituents in Duzhong Jiangya tablet, lay a foundation for the research on the efficacy and quality of this traditional Chinese medicine, and provide a reference for the characterization of the chemical constituents of other traditional Chinese medicine preparations.

Chemical constituents, cytotoxic activities and traditional uses of Micromelum minutum (Rutaceae): a review

Micromelum minutum belongs to the family of aromatic deciduous trees and shrubs Rutaceae Different types of coumarins together with two alkaloids are found in the plant Chemical constituents are isolate from different parts of the plant leaves stem stem bark fruits seeds and roots Traditionally the plant is used for various purposes Scientific investigations particularly focused on the cytotoxicity of the plant The reviews compile the botanical description traditional use chemical constituents and cytitoxic activities of Micromelum minutum

Synthesis, Transformations and Characterization of 8 Aminomethyl Substituted Umbelliferones as Probable Anti-Arrhythmic Agents

Background: Coumarin and modified nitrogen heterocyclic nuclei show biological activity. Combining these into a hybrid molecule could lead to new pharmacological agents. A series of hybrid compounds combining coumarin and piperidine, piperazine, purine or tetrahydroisoquinoline moieties were synthesized and evaluated for anti-arrhythmic activity. Methods: The Mannich reaction of coumarins (peurutenicin, peucenol and 6-cyanoumbelliferrone) with formaldehyde and various amines, including several alkaloids – anabasine, theophylline or tetrahydroisoquinolines, proceeds by heating under reflux in dioxane in the presence of 4-dimethylaminopyridine. The Suzuki reaction of 6,8-disubstituted umbelliferone triflate was used for the introduction of an aryl substituent in position 7 of the the coumarin framework. Results: Twenty two novel coumarin-based Mannich bases were synthesized via introduction of functional aminomethyl group at position 8 of 6 substituted 7-hydroxy-2H-chromen-2-ones by Mannich reaction. The results illustrated that the C-6 and C-8 substituents’ effect was obvious in our designed system and there was a relationship between the structures and the anti-arrhythmic activity of the 6,7,8- trisubstituted coumarins. 8-(6,7-dimethoxy-1-(3,4,5-trimethoxyphenyl)-tetrahydroisoquinolinylmethyl)- substituted peucenol derivatives shown in vivo a pronounced and selective anti-arrhythmic activity on epinephrine arrhythmias in comparison with natural coumarin peucenol. The moderate toxicity of the new compound encouraged further design of therapeutically relevant analogues based on this novel type of coumarin- tetrahydroisoquinoline hybrids. Conclusion: We have developed a mild reaction protocol to synthesize new mannich products on the basis of substituted coumarins. The anti-arrhythmic activity of coumarin-tetrahydroisoquinoline hybrids was revealed. We report for the first time that coumarin containing 8-(1-(3,4,5-trimethoxyphenyl) tetrahydroisoquinolinyl)methyl) substituent offer a suitable scaffold for the development of novel anti-arrhythmic agents.