RESUMO
Neurotrophins such as nerve growth factor (ngf) and brain-derived neurotrophic factor (bdnf) play important roles in the central nervous system. They are potential therapeutic drugs for the treatment of neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. In this study, we investigated the neurotrophic properties of triterpenes isolated from fruiting bodies of Laetiporus sulphureus and a mycelial culture of Antrodia sp. MUCL 56049. The structures of the isolated compounds were elucidated based on nuclear magnetic resonance (NMR) spectroscopy in combination with high-resolution electrospray mass spectrometry (HR-ESIMS). The secondary metabolites were tested for neurotrophin (ngf and bdnf) expression levels on human astrocytoma 1321N1 cells. Neurite outgrowth activity using rat pheochromocytoma (PC-12) cells was also determined. Twelve triterpenoids were isolated, of which several potently stimulated the expression of neurotrophic factors, namely, ngf (sulphurenic acid, 15α-dehydroxytrametenolic acid, fomefficinic acid D, and 16α-hydroxyeburicoic acid) and bdnf (sulphurenic acid and 15α-dehydroxytrametenolic acid), respectively. The triterpenes also potentiated ngf-induced neurite outgrowth in PC-12 cells. This is, to the best of our knowledge, the first report on the compound class of lanostanes in direct relation to bdnf and ngf enhancement. These compounds are widespread in medicinal mushrooms; hence, they appear promising as a starting point for the development of drugs and mycopharmaceuticals to combat neurodegenerative diseases. Interestingly, they do not show any pronounced cytotoxicity and may, therefore, be better suited for therapy than many other neurotrophic compounds that were previously reported.
Assuntos
Basidiomycota , Doenças Neurodegenerativas , Triterpenos , Animais , Ratos , Humanos , Fator de Crescimento Neural/farmacologia , Fator de Crescimento Neural/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Triterpenos/farmacologia , Triterpenos/química , Madeira/metabolismo , Basidiomycota/químicaRESUMO
Burkholderia encompasses a group of ubiquitous Gram-negative bacteria that includes numerous saprophytes as well as species that cause infections in animals, immunocompromised patients, and plants. Some species of Burkholderia produce colored, redox-active secondary metabolites called phenazines. Phenazines contribute to competitiveness, biofilm formation, and virulence in the opportunistic pathogen Pseudomonas aeruginosa, but knowledge of their diversity, biosynthesis, and biological functions in Burkholderia is lacking. In this study, we screened publicly accessible genome sequence databases and identified phenazine biosynthesis genes in multiple strains of the Burkholderia cepacia complex, some isolates of the B. pseudomallei clade, and the plant pathogen B. glumae We then focused on B. lata ATCC 17760 to reveal the organization and function of genes involved in the production of dimethyl 4,9-dihydroxy-1,6-phenazinedicarboxylate. Using a combination of isogenic mutants and plasmids carrying different segments of the phz locus, we characterized three novel genes involved in the modification of the phenazine tricycle. Our functional studies revealed a connection between the presence and amount of phenazines and the dynamics of biofilm growth in flow cell and static experimental systems but at the same time failed to link the production of phenazines with the capacity of Burkholderia to kill fruit flies and rot onions.IMPORTANCE Although the production of phenazines in Burkholderia was first reported almost 70 years ago, the role these metabolites play in the biology of these economically important microorganisms remains poorly understood. Our results revealed that the phenazine biosynthetic pathway in Burkholderia has a complex evolutionary history, which likely involved horizontal gene transfers among several distantly related groups of organisms. The contribution of phenazines to the formation of biofilms suggests that Burkholderia, like fluorescent pseudomonads, may benefit from the unique redox-cycling properties of these versatile secondary metabolites.
Assuntos
Proteínas de Bactérias/genética , Biofilmes/crescimento & desenvolvimento , Burkholderia/fisiologia , Genoma Bacteriano , Fenazinas/metabolismo , Proteínas de Bactérias/metabolismo , Burkholderia/genéticaRESUMO
Histone posttranslational modifications (HPTMs) are involved in chromatin-based regulation of fungal secondary metabolite biosynthesis (SMB) in which the corresponding genes-usually physically linked in co-regulated clusters-are silenced under optimal physiological conditions (nutrient-rich) but are activated when nutrients are limiting. The exact molecular mechanisms by which HPTMs influence silencing and activation, however, are still to be better understood. Here we show by a combined approach of quantitative mass spectrometry (LC-MS/MS), genome-wide chromatin immunoprecipitation (ChIP-seq) and transcriptional network analysis (RNA-seq) that the core regions of silent A. nidulans SM clusters generally carry low levels of all tested chromatin modifications and that heterochromatic marks flank most of these SM clusters. During secondary metabolism, histone marks typically associated with transcriptional activity such as H3 trimethylated at lysine-4 (H3K4me3) are established in some, but not all gene clusters even upon full activation. KdmB, a Jarid1-family histone H3 lysine demethylase predicted to comprise a BRIGHT domain, a zinc-finger and two PHD domains in addition to the catalytic Jumonji domain, targets and demethylates H3K4me3 in vivo and mediates transcriptional downregulation. Deletion of kdmB leads to increased transcription of about ~1750 genes across nutrient-rich (primary metabolism) and nutrient-limiting (secondary metabolism) conditions. Unexpectedly, an equally high number of genes exhibited reduced expression in the kdmB deletion strain and notably, this group was significantly enriched for genes with known or predicted functions in secondary metabolite biosynthesis. Taken together, this study extends our general knowledge about multi-domain KDM5 histone demethylases and provides new details on the chromatin-level regulation of fungal secondary metabolite production.
Assuntos
Aspergillus nidulans/genética , Histona Desmetilases/genética , Histona Desmetilases com o Domínio Jumonji/genética , Metabolismo Secundário/genética , Aspergillus nidulans/metabolismo , Cromatina/genética , Metilação de DNA/genética , Regulação Fúngica da Expressão Gênica , Genoma , Histona Desmetilases/metabolismo , Histonas/metabolismo , Humanos , Histona Desmetilases com o Domínio Jumonji/metabolismo , Espectrometria de Massas em TandemRESUMO
BACKGROUND: Within the polymicrobial dental plaque biofilm, bacteria kill competitors by excreting mixtures of bacteriocins, resulting in improved fitness and survival. Inhibiting their bacteriocin synthesis might therefore be a useful strategy to eliminate specific pathogens. We used Streptococcus mutans, a highly acidogenic inhabitant of dental plaque, as a model and searched for natural products that reduced mutacin synthesis. To this end we fused the promoter of mutacin VI to the GFP+ gene and integrated the construct into the genome of S. mutans UA159 by single homologous recombination. RESULTS: The resulting reporter strain 423p - gfp + was used to screen 297 secondary metabolites from different sources, mainly myxobacteria and fungi, for their ability to reduce the fluorescence of the fully induced reporter strain by > 50% while growth was almost unaffected (> 90% of control). Seven compounds with different chemical structures and different modes of action were identified. Erinacine C was subsequently validated and shown to inhibit transcription of all three mutacins of S. mutans. The areas of the inhibition zones of the sensor strains S. sanguinis and Lactococcus lactis were reduced by 35% to 61% in comparison to controls in the presence of erinacine C, demonstrating that the amount of active mutacins in the culture supernatants of S. mutans was reduced. Erinacines are cyathane diterpenes that were extracted from cultures of the edible mushroom Hericium erinaceus. They have anti-inflammatory, antimicrobial and neuroprotective effects. For erinacine C, a new biological activity was found here. CONCLUSIONS: We demonstrate the successful development of a whole-cell fluorescent reporter for the screening of natural compounds and report that erinacine C suppresses mutacin synthesis in S. mutans without affecting cell viability.
Assuntos
Antibacterianos/farmacologia , Bacteriocinas/biossíntese , Diterpenos/farmacologia , Streptococcus mutans/efeitos dos fármacos , Streptococcus mutans/metabolismo , Agaricales/química , Anti-Inflamatórios/farmacologia , Bacteriocinas/genética , Basidiomycota/química , Biofilmes , Placa Dentária/microbiologia , Escherichia coli/genética , Fluorescência , Genes Bacterianos/genética , Recombinação Homóloga , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Regiões Promotoras Genéticas , Metabolismo Secundário , Deleção de Sequência , Streptococcus mutans/genética , Streptococcus mutans/crescimento & desenvolvimento , Transcrição Gênica/efeitos dos fármacosRESUMO
Basidiomycetes of the genus Hericium are among the most praised medicinal and edible mushrooms, which are known to produce secondary metabolites with the potential to treat neurodegenerative diseases. This activity has been attributed to the discovery of various terpenoids that can stimulate the production of nerve growth factor (NGF) or (as established more recently) brain-derived neurotrophic factor (BDNF) in cell-based bioassays. The present study reports on the metabolite profiles of a Lion's Mane mushroom (Hericium erinaceus) strain and a strain of the rare species, Hericium flagellum (synonym H. alpestre). While we observed highly similar metabolite profiles between the two strains that were examined, we isolated two previously undescribed metabolites, given the trivial names erinacines Z1 and Z2. Their chemical structures were elucidated by means of nuclear magnetic resonance (NMR) spectroscopy and high resolution mass spectrometry. Along with six further, previously identified cyathane diterpenes, the novel erinacines were tested for neurotrophin inducing effects. We found that erinacines act on BDNF, which is a neurotrophic factor that has been reported recently by us to be induced by the corallocins, but as well on NGF expression, which is consistent with the literature.
Assuntos
Basidiomycota/química , Produtos Biológicos/química , Diterpenos/química , Animais , Produtos Biológicos/farmacologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Diferenciação Celular/efeitos dos fármacos , Diterpenos/farmacologia , Humanos , Micélio/química , Células PC12 , RatosRESUMO
Bioassay-guided fractionation of the mycelial extract of a basidiomycete culture collected in Kenya led to the isolation of two new cyathane diterpenoids named laxitextines A (1) and B (2). The producer strain was characterized by detailed taxonomic studies based on rDNA using the 5.8S gene region, the internal transcribed spacer 2 (ITS2), and part of the large subunit that identified the fungus as Laxitextum incrustatum. The structures of 1 and 2 were elucidated by NMR spectroscopic and mass spectrometric analyses. Both compounds exhibited moderate activities against Gram-positive bacteria Bacillus subtilis (DSM 10), Staphylococcus aureus (DSM 346), and methicillin-resistant Staph. aureus (DSM 1182). The two compounds also showed variable antiproliferative activities against mouse fibroblast (L929) and selected human cell lines (breast cancer MCF-7, epidermoid carcinoma A431, and umbilical vein endothelial HUVEC). The IC50 values with respect to the MCF-7 cell line for compounds 1 and 2 were 2.3 and 2.0 µM, respectively.
Assuntos
Antibacterianos/isolamento & purificação , Antineoplásicos/isolamento & purificação , Diterpenos/isolamento & purificação , Glicosídeos/isolamento & purificação , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Bacillus subtilis/efeitos dos fármacos , Diterpenos/química , Diterpenos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Glicosídeos/química , Glicosídeos/farmacologia , Humanos , Células MCF-7 , Resistência a Meticilina/efeitos dos fármacos , Camundongos , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Staphylococcus aureus/efeitos dos fármacosRESUMO
Three new natural products, corallocins A-C (1-3), along with two known compounds were isolated from the mushroom Hericium coralloides. Their benzofuranone and isoindolinone structures were elucidated by spectral methods. All corallocins induced nerve growth factor and/or brain-derived neurotrophic factor expression in human 1321N1 astrocytes. Furthermore, corallocin B showed antiproliferative activity against HUVEC and human cancer cell lines MCF-7 and KB-3-1.
Assuntos
Agaricales/química , Benzofuranos/isolamento & purificação , Benzofuranos/farmacologia , Fator Neurotrófico Derivado do Encéfalo/agonistas , Fatores de Crescimento Neural/agonistas , Animais , Astrócitos/efeitos dos fármacos , Benzofuranos/química , Alemanha , Humanos , Estrutura Molecular , Proteínas do Tecido Nervoso , Ressonância Magnética Nuclear Biomolecular , Células PC12 , RatosRESUMO
Current treatment of Chlamydia trachomatis using doxycycline and azithromycin introduces detrimental side effects on the host's microbiota. As a potential alternative treatment, the myxobacterial natural product sorangicin A (SorA) blocks the bacterial RNA polymerase. In this study we analyzed the effectiveness of SorA against C. trachomatis in cell culture, and explanted fallopian tubes and systemic and local treatment in mice, providing also pharmacokinetic data on SorA. Potential side effects of SorA on the vaginal and gut microbiome were assessed in mice and against human-derived Lactobacillus species. SorA showed minimal inhibitory concentrations of 80 ng/mL (normoxia) to 120 ng/mL (hypoxia) against C. trachomatis in vitro and was eradicating C. trachomatis at a concentration of 1 µg/mL from fallopian tubes. In vivo, SorA reduced chlamydial shedding by more than 100-fold within the first days of infection by topical application corresponding with vaginal detection of SorA only upon topical treatment, but not after systemic application. SorA changed gut microbial composition during intraperitoneal application only and did neither alter the vaginal microbiota in mice nor affect growth of human-derived lactobacilli. Additional dose escalations and/or pharmaceutical modifications will be needed to optimize application of SorA and to reach sufficient anti-chlamydial activity in vivo.
RESUMO
In our continued search for biologically active metabolites from cultures of rare Basidiomycota species, we found eight previously undescribed cyathane-xylosides from submerged cultures of Dentipellis fragilis, which were named dentifragilins A-H. In addition, the known cyathane derivatives striatal D and laxitextine A were isolated. All compounds were characterized by high-resolution electrospray ionization mass spectrometry (HR-ESIMS) as well as by 1D and 2D nuclear magnetic resonance (NMR) spectroscopy. Several of the compounds exhibited significant activities in standardized cell-based assays for the determination of antimicrobial and cytotoxic effects. The discovery of cyathanes in the genus Dentipellis has chemotaxonomic implications, as this class of diterpenoids has already been shown to be characteristic for mycelial cultures of the related genera Hericium and Laxitextum, which are classified as Dentipellis in the family Hericiaceae.
RESUMO
Medicinal mushrooms of the genus Hericium are known to produce secondary metabolites with homeostatic properties for the central nervous system. We and others have recently demonstrated that among these metabolites cyathane diterpenoids and in particular erinacine C possess potent neurotrophin inducing properties in astrocytic cells. Yet, the signaling events downstream of erinacine C induced neurotrophin acitivity in neural-like adrenal phaeochromocytoma cells (PC12) cells have remained elusive. Similar, signaling events activated by erinacine C in astrocytic cells are unknown. Using a combination of genetic and pharmacological inhibitors we show that erinacine C induced neurotrophic activity mediates PC12 cell differentiation via the TrkA receptor and likely its associated PLCγ-, PI3K-, and MAPK/ERK pathways. Furthermore, a small library of transcriptional activation reporters revealed that erinacine C induces transcriptional activation mediated by DNA consensus binding sites of selected conserved transcription factor families. Among these, transcription is activated from an ETS consensus in a concentration dependent manner. Interestingly, induced ETS-consensus transcription occurs in parallel and independent of neurotrophin induction. This finding helps to explain the many pleiotropic functions of cyathane diterpenoids. Moreover, our studies provide genetic access to cyathane diterpenoid functions in astrocytic cells and help to mechanistically understand the action of cyathanes in glial cells.
Assuntos
Astrócitos/efeitos dos fármacos , Diterpenos/farmacologia , Ativação Transcricional/efeitos dos fármacos , Animais , Astrócitos/fisiologia , Sítios de Ligação/genética , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Células Cultivadas , Sequência Conservada/efeitos dos fármacos , Sequência Conservada/genética , Motivo ETS , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/genética , Fator de Crescimento Neural/genética , Fator de Crescimento Neural/metabolismo , Células PC12 , Ligação Proteica/efeitos dos fármacos , Ligação Proteica/genética , Ratos , Fatores de Transcrição/química , Fatores de Transcrição/metabolismo , Ativação Transcricional/genética , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genéticaRESUMO
BACKGROUND: Hepatocellular carcinoma (HCC) represents a major health burden with limited curative treatment options. There is a substantial unmet need to develop innovative approaches to impact the progression of advanced HCC. Haprolid is a novel natural component isolated from myxobacteria. Haprolid has been reported as a potent selective cytotoxin against a panel of tumor cells in recent studies including HCC cells. The aims of this study are to evaluate the antitumor effect of haprolid in HCC and to understand its underlying molecular mechanisms. METHODS: The efficacy of haprolid was evaluated in human HCC cell lines (Huh-7, Hep3B and HepG2) and xenograft tumors (NMRI-Foxn1nu mice with injection of Hep3B cells). Cytotoxic activity of haprolid was determined by the WST-1 and crystal violet assay. Wound healing, transwell and tumorsphere assays were performed to investigate migration and invasion of HCC cells. Apoptosis and cell-cycle distribution were measured by flow cytometry. The effects of haprolid on the Rb/E2F and Akt/mTOR pathway were examined by immunoblotting and immunohistochemistry. RESULTS: haprolid treatment significantly inhibited cell proliferation, migration and invasion in vitro. The epithelial-mesenchymal transition (EMT) was impaired by haprolid treatment and the expression level of N-cadherin, vimentin and Snail was downregulated. Moreover, growth of HCC cells in vitro was suppressed by inhibition of G1/S transition, and partially by induction of apoptosis. The drug induced downregulation of cell cycle regulatory proteins cyclin A, cyclin B and CDK2 and induced upregulation of p21 and p27. Further evidence showed that these effects of haprolid were associated with Rb/E2F downregulation and Akt/mTOR inhibition. Finally, in vivo nude mice experiments demonstrated significant inhibition of tumor growth upon haprolid treatment. CONCLUSION: Our results show that haprolid inhibits the growth of HCC through dual inhibition of Rb/E2F and Akt/mTOR pathways. Therefore, haprolid might be considered as a new and promising candidate for the palliative therapy of HCC.
RESUMO
Chemical analysis of extracts from cultures of the plant pathogenic fungus Cytospora sp. strain CCTU A309 collected in Iran led to the isolation of two previously unreported heptanedioic acid derivatives namely (2R,3S) 2-hydroxy-3-phenyl-4-oxoheptanedioic acid (1) and (2S,3S) 2-hydroxy-3-phenyl-4-oxoheptanedioic acid (2) as diastereomers, four previously undescribed prenylated p-terphenyl quinones 3-6 in addition to five known metabolites. Their structures were elucidated on the basis of extensive spectroscopic analysis and high-resolution mass spectrometry. For metabolites 1 and 2, the absolute configurations at C-2 were deduced from comparison of the 1H NMR difference of their (S)- and (R)-phenylglycine methyl ester derivatives while the relative configurations were tentatively assigned by a J-based analysis and confirmed by comparison of 13C chemical shifts to literature data. The isolated compounds were tested for their cytotoxic, antimicrobial (including biofilm inhibition), antiviral, and nematicidal activities. While only moderate antimicrobial effects were observed, the terphenyl quinone derivatives 3-6 and leucomelone (10) exhibited significant cytotoxicity against the mouse fibroblast L929 and cervix carcinoma KB-3-1 cell lines with IC50 values ranging from 2.4 to 26⯵g/mL. Furthermore, metabolites 4-6 showed interesting antiviral activity against hepatitis C virus (HCV).
Assuntos
Antibacterianos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Antivirais/farmacologia , Ascomicetos/química , Quinonas/farmacologia , Compostos de Terfenil/farmacologia , Animais , Antibacterianos/isolamento & purificação , Antineoplásicos Fitogênicos/isolamento & purificação , Antivirais/isolamento & purificação , Linhagem Celular Tumoral , Humanos , Irã (Geográfico) , Camundongos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Quinonas/isolamento & purificação , Metabolismo Secundário , Compostos de Terfenil/isolamento & purificaçãoRESUMO
Fermentation of the fungal strain Skeletocutis sp. originating from Mount Elgon Natural Reserve in Kenya, followed by bioassay guided fractionation led to the isolation of 12 previously undescribed metabolites named skeletocutins A-L (1-5 and 7-13) together with the known tyromycin A (6). Their structures were assigned by NMR spectroscopy complemented by HR-ESIMS. Compounds 1-6 and 11-13 exhibited selective activities against Gram-positive bacteria, while compound 10 weakly inhibited the formation of biofilm of Staphylococcus aureus. The isolated metabolites were also evaluated for inhibition of L-leucine aminopeptidase, since tyromycin A had previously been reported to possess such activities but only showed weak effects. Furthermore, all compounds were tested for antiviral activity against Hepatitis C virus (HCV), and compound 6 moderately inhibited HCV infectivity with an IC50 of 6.6 µM.
Assuntos
Antibacterianos/farmacologia , Polyporales/química , Madeira/microbiologia , Antibacterianos/química , Antibacterianos/metabolismo , Antivirais/química , Antivirais/metabolismo , Antivirais/farmacologia , Hepacivirus/efeitos dos fármacos , Quênia , Testes de Sensibilidade Microbiana , Estrutura Molecular , Polyporales/crescimento & desenvolvimento , Polyporales/isolamento & purificação , Polyporales/metabolismoRESUMO
During the course of our ongoing work to discover new inhibitors of biofilm formation of Staphylococcus aureus from fungal sources, we observed biofilm inhibition by cytochalasans isolated from cultures of the ascomycete Hypoxylon fragiforme for the first time. Two new compounds were purified by a bioassay-guided fractionation procedure; their structures were elucidated subsequently by nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry (HR-MS). This unexpected finding prompted us to test further cytochalasans from other fungi and from commercial sources for comparison. Out of 21 cytochalasans, 13 showed significant inhibition of Staphylococcus aureus biofilm formation at subtoxic levels. These findings indicate the potential of cytochalasans as biofilm inhibitors for the first time, also because the minimum inhibitory concentrations (MIC) are independent of the anti-biofilm activities. However, cytochalasans are known to be inhibitors of actin, making some of them very toxic for eukaryotic cells. Since the chemical structures of the tested compounds were rather diverse, the inclusion of additional derivatives, as well as the evaluation of their selectivity against mammalian cells vs. the bacterium, will be necessary as next step in order to develop structure-activity relationships and identify the optimal candidates for development of an anti-biofilm agent.
Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Staphylococcus aureus/fisiologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Fungos/química , Espectroscopia de Ressonância Magnética , MetabolomaRESUMO
Complexity-generating chemical transformations that afford novel molecular scaffolds enriched in sp3 character are highly desired. Here, we present a highly stereoselective scaffold diversity synthesis approach that utilizes cascade double-annulation reactions of diverse pairs of zwitterionic and non-zwitterionic partners with 3-formylchromones to generate highly complex tetracyclic benzopyrones. Each pair of annulation partners adds to the common chroman-4-one scaffold to build two new rings, supporting up to four contiguous chiral centers that include an all-carbon quaternary center. Differently ring-fused benzopyrones display different biological activities, thus demonstrating their immense potential in medicinal chemistry and chemical biology research.
RESUMO
Amanita ballerina and A. brunneitoxicaria spp. nov. are introduced from Thailand. Amanita fuligineoides is also reported for the first time from Thailand, increasing the known distribution of this taxon. Together, those findings support our view that many taxa are yet to be discovered in the region. While both morphological characters and a multiple-gene phylogeny clearly place A. brunneitoxicaria and A. fuligineoides in sect. Phalloideae (Fr.) Quél., the placement of A. ballerina is problematic. On the one hand, the morphology of A. ballerina shows clear affinities with stirps Limbatula of sect. Lepidella. On the other hand, in a multiple-gene phylogeny including taxa of all sections in subg. Lepidella, A. ballerina and two other species, including A. zangii, form a well-supported clade sister to the Phalloideae sensu Bas 1969, which include the lethal "death caps" and "destroying angels". Together, the A. ballerina-A. zangii clade and the Phalloideae sensu Bas 1969 also form a well-supported clade. We therefore screened for two of the most notorious toxins by HPLC-MS analysis of methanolic extracts from the basidiomata. Interestingly, neither α-amanitin nor phalloidin was found in A. ballerina, whereas Amanita fuligineoides was confirmed to contain both α-amanitin and phalloidin, and A. brunneitoxicaria contained only α-amanitin. Together with unique morphological characteristics, the position in the phylogeny indicates that A. ballerina is either an important link in the evolution of the deadly Amanita sect. Phalloideae species, or a member of a new section also including A. zangii.
Assuntos
Amanita/classificação , DNA Fúngico/análise , Micotoxinas/isolamento & purificação , Alfa-Amanitina/isolamento & purificação , Amanita/genética , Amanita/metabolismo , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas , Micotoxinas/classificação , Faloidina/isolamento & purificação , Filogenia , Análise de Sequência de DNA , TailândiaAssuntos
Éteres/química , Ouro/química , Alcinos/química , Catálise , Ciclização , Éteres/síntese química , Estereoisomerismo , Estirenos/químicaRESUMO
A cascade double-annulation strategy employing diverse pairs of zwitterions with 3-formylchromones is presented that provides stereoselective access to complex tetracyclic benzopyrones. Different zwitterions incorporated different rings that include aza-, oxa-, and carbocycles fused to a common benzopyrone scaffold and in the process created three contiguous chiral centers including an all-carbon-quaternary center with high efficiency and excellent stereoselectivity.
Assuntos
Compostos Heterocíclicos de 4 ou mais Anéis/síntese química , Pironas/síntese química , Ciclização , Compostos Heterocíclicos de 4 ou mais Anéis/química , Estrutura Molecular , Pironas/química , EstereoisomerismoRESUMO
A silver catalyzed and microwave assisted one-pot cascade synthesis provides efficient access to diverse alkaloid-inspired scaffold classes, and a concise and efficient total synthesis of homofascaplysin C and fascaplysin.