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1.
Nat Prod Res ; 34(4): 464-473, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30257108

RESUMO

A new cyclic pentapeptide, pentaminolarin (1), and a new cytochalasin, xylochalasin (2), along with thirteen known compounds (3-15) were isolated from the wood-decaying fungus Xylaria sp. SWUF08-37. The absolute configurations of 1 were determined by a combination of Marfey's method and TDDFT ECD calculation and the absolute configurations of 2 were established by TDDFT ECD calculation. Compound 12 showed moderate cytotoxicity against HeLa (IC50 = 19.60 µg/mL), HT29 (IC50 = 17.31 µg/mL), HCT116 (IC50 = 14.28 µg/mL), MCF-7 (IC50 = 15.38 µg/mL), and Vero (IC50 = 24.97 µg/mL) cell lines by MTT assay. Compounds 1 and 2 showed slight cytotoxicity against all tested cancer cell lines.


Assuntos
Antineoplásicos/isolamento & purificação , Citocalasinas/isolamento & purificação , Peptídeos Cíclicos/isolamento & purificação , Xylariales/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Citocalasinas/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Conformação Molecular , Peptídeos Cíclicos/farmacologia , Xylariales/patogenicidade
2.
Molecules ; 24(18)2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31492021

RESUMO

Two new cytochalasans, Chaetomadrasins A (1) and B (2), along with six known analogues (3-8), were isolated from the solid-state fermented culture of desert soil-derived Chaetomium madrasense 375. Their structures were clarified by comprehensive spectroscopic analyses, and the absolute configurations of Compounds 1 and 2 were confirmed by electronic circular dichroism (ECD) and calculated ECD. For the first time, Chaetomadrasins A (1), which belongs to the chaetoglobosin family, is characterized by the presence of all oxygen atoms in the form of Carbonyl. Chaetomadrasin B (2) represents the first example of chaetoglobosin type cytochalasan characterized by a hydroxy unit and carbonyl group fused to the indole ring. Compounds 1 and 2 displayed moderate cytotoxicity against HepG2 human hepatocellular carcinoma cells.


Assuntos
Antineoplásicos/farmacologia , Produtos Biológicos/farmacologia , Chaetomium/química , Citocalasinas/farmacologia , Microbiologia do Solo , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Linhagem Celular , Citocalasinas/química , Citocalasinas/isolamento & purificação , Humanos , Modelos Moleculares , Conformação Molecular , Estrutura Molecular , Análise Espectral
3.
Org Biomol Chem ; 17(34): 7985-7994, 2019 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-31408074

RESUMO

Eleven new cytochalasins, curtachalasins F-P (1-11), were isolated from the rice fermentation of endophytic fungus Xylaria cf. curta. Their structures were identified by extensive spectroscopic methods, X-ray diffraction, and quantum chemistry calculations. Curtachalasin P possesses a unique 5/6/6/7 fused ring system. In the bioactivity screening for curtachalasins F-P, A-C, and E (1-15), compounds 1, 3-6, 8-13, and 15 did not show obvious cytotoxicity against primary mouse splenocytes. Furthermore, the immunosuppressive assay against concanavalin A (ConA) induced T lymphocyte cell proliferation and lipopolysaccharide (LPS) induced B lymphocyte cell proliferation showed that compound 1 results in significant selective inhibition on B-cell proliferation (IC50 value of 2.42 µM) and compound 10 has selective inhibition on T-cell proliferation (IC50 value of 12.15 µM). These interesting immunosuppressive properties of this class of compounds provide new clues to fulfill the urgent demand for new immunosuppressive drugs.


Assuntos
Citocalasinas/farmacologia , Imunossupressores/farmacologia , Xylariales/química , Animais , Linfócitos B/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Citocalasinas/química , Citocalasinas/isolamento & purificação , Imunossupressores/química , Imunossupressores/isolamento & purificação , Masculino , Camundongos Endogâmicos BALB C , Estrutura Molecular , Linfócitos T/efeitos dos fármacos
4.
Fitoterapia ; 137: 104278, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31351910

RESUMO

Five new cytochalasans (1-5) were isolated from the rice fermentation of fungus Xylaria longipes, along with seven known compounds cytochalasin P (6), cytochalasin D (7), zygosporin D (8), 7-O-acetylcytochalasin D (9), cytochalasin C (10), 6,7-dihydro-7-oxo-cytochalasin C (11), and 6,7-dihydro-7-oxo-deacetylcytochalasin C (12). Their structures and absolute configurations were determined by extensive experimental spectroscopic methods as well as ECD calculation and GIAO 13C NMR calculation. The cytotoxicity of obtained compounds (1-12) was evaluated against human cancer cell lines HL-60, A549, SMMC-7721, MCF-7, and SW480. Compounds 6-8, 11, and 12 showed cytotoxicity with IC50 value ranging from 4.17-37.18 µM.


Assuntos
Antineoplásicos/farmacologia , Citocalasinas/farmacologia , Xylariales/química , Antineoplásicos/isolamento & purificação , Linhagem Celular Tumoral , China , Citocalasinas/isolamento & purificação , Humanos , Estrutura Molecular , Metabolismo Secundário
5.
Fitoterapia ; 137: 104253, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31271786

RESUMO

Nine new 19,20-epoxycytochalasans (1-9) were isolated from the rice fermentation extracts of endophytic fungus Xylaria cf. curta, along with four known compounds 19,20-epoxycytochalasin C (10), 18-desoxy-19,20-epoxycytochalasin C (11), 19,20-epoxycytochalasin D (12) and 5,6-dihydro-7-oxo-19,20-epoxycytochalasin C (13). Their structures and absolute configurations were determined by 1D and 2D NMR, HRESIMS, X-ray diffraction and ECD calculation. The cytotoxicity of obtained compounds (1-13) was evaluated against human cancer cell lines HL-60, A549, SMMC-7721, MCF-7, and SW480. Remarkably, compound 10 showed significant specific cytotoxicity against HL-60 cell lines with IC50 value of 1.11 µM.


Assuntos
Antineoplásicos/farmacologia , Citocalasinas/farmacologia , Xylariales/química , Antineoplásicos/isolamento & purificação , Linhagem Celular Tumoral , Citocalasinas/isolamento & purificação , Endófitos/química , Humanos , Estrutura Molecular
6.
Fitoterapia ; 137: 104187, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31153951

RESUMO

Four new compounds: diaporthichalasins A-C (1-3) and biatriosporin N (7), along with six known compounds (4-6 and 8-10) were separated from the culture of the fungus Diaporthe sp. GZU-1021. The absolute configurations of 1-3 were determined by quantum chemical calculations, X-ray diffraction, and spectroscopic analysis. The structure of 4 was analyzed by X-ray crystallography analysis for the first time. All of the isolates were evaluated on the production of nitric oxide in lipopolysaccharide-induced microglial cells (RAW 264.7 cells). Compounds 5-10 exhibited significant inhibitory effects against nitric oxide production with IC50 values from 1.94 to 16.5 µM than positive control (indomethacin, IC50 = 29.7 µM). This is the first time tetrahydroxanthone dimer (10), as a novel carbon skeleton possessing NO inhibitory activity, was reported.


Assuntos
Anti-Inflamatórios/farmacologia , Ascomicetos/química , Citocalasinas/farmacologia , Microglia/efeitos dos fármacos , Policetídeos/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Braquiúros/microbiologia , China , Citocalasinas/isolamento & purificação , Camundongos , Estrutura Molecular , Óxido Nítrico/metabolismo , Policetídeos/isolamento & purificação , Células RAW 264.7
7.
J Agric Food Chem ; 67(13): 3643-3650, 2019 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-30875204

RESUMO

Bioactivity-guided isolation of the cultures of the endophytic fugus Xylaria sp. XC-16 residing in a deciduous tree Toona sinensis led to the discovery of four new allelochemicals (1-4), including three cytochalasins, epoxycytochalasin Z17 (1), epoxycytochalasin Z8 (2), and epoxyrosellichalasin (3), and an abietane-type diterpenoid, hydroxyldecandrin G (4), along with four known analogues, 10-phenyl-[12]-cytochalasins Z16 (5) and Z17 (6), cytochalasin K (7), and cytochalasin E (8). The structures of these compounds were elucidated by comprehensive spectroscopic methods, and their absolute configurations were determined by electronic circular dichroism (CD) and X-ray diffraction. All of the chemicals were tested for their allelopathic effects on turnip ( Raphanus sativus) and wheat ( Triticum aestivum). Notably, compounds 3, 4, and 7 strongly inhibited wheat shoot elongation, and compounds 5, 7, and 8 inhibited wheat root elongation, showing comparable IC50 values to the positive control glyphosate. Meanwhile, compound 8 was a potential inhibitor on turnip root elongation, with an IC50 value of 1.57 ± 0.21 µM, which was 50-fold more potent than glyphosate. Nevertheless, compounds 5 and 7 stimulated turnip shoot elongation at lower concentrations.


Assuntos
Abietanos/farmacologia , Citocalasinas/farmacologia , Endófitos/química , Meliaceae/microbiologia , Xylariales/química , Abietanos/química , Alelopatia , Brassica napus/efeitos dos fármacos , Brassica napus/crescimento & desenvolvimento , Citocalasinas/química , Estrutura Molecular , Triticum/efeitos dos fármacos , Triticum/crescimento & desenvolvimento
8.
Molecules ; 24(4)2019 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-30795572

RESUMO

Bioassay-guided fractionation of an EtOAc extract of the broth of the endophytic fungus Nemania sp. UM10M (Xylariaceae) isolated from a diseased Torreya taxifolia leaf afforded three known cytochalasins, 19,20-epoxycytochalasins C (1) and D (2), and 18-deoxy-19,20-epoxy-cytochalasin C (3). All three compounds showed potent in vitro antiplasmodial activity and phytotoxicity with no cytotoxicity to Vero cells. These compounds exhibited moderate to weak cytotoxicity to some of the cell lines of a panel of solid tumor (SK-MEL, KB, BT-549, and SK-OV-3) and kidney epithelial cells (LLC-PK11). Evaluation of in vivo antimalarial activity of 19,20-epoxycytochalasin C (1) in a mouse model at 100 mg/kg dose showed that this compound had weak suppressive antiplasmodial activity and was toxic to animals.


Assuntos
Antineoplásicos/farmacologia , Antiprotozoários/farmacologia , Citocalasinas/farmacologia , Malária/tratamento farmacológico , Taxaceae/microbiologia , Xylariales/química , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antiprotozoários/química , Antiprotozoários/isolamento & purificação , Linhagem Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Chlorocebus aethiops , Citocalasinas/química , Citocalasinas/isolamento & purificação , Endófitos/química , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Humanos , Malária/mortalidade , Malária/parasitologia , Masculino , Camundongos , Folhas de Planta/microbiologia , Plasmodium berghei/efeitos dos fármacos , Plasmodium berghei/crescimento & desenvolvimento , Análise de Sobrevida , Células Vero
9.
Biomolecules ; 9(2)2019 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-30791504

RESUMO

In our ongoing search for new bioactive fungal metabolites, two new cytochalasans were isolated from stromata of the hypoxylaceous ascomycete Hypoxylon fragiforme. Their structures were elucidated via high-resolution mass spectrometry (HR-MS) and nuclear magnetic resonance (NMR) spectroscopy. Together with 23 additional cytochalasans isolated from ascomata and mycelial cultures of different Ascomycota, they were tested on their ability to disrupt the actin cytoskeleton of mammal cells in a preliminary structure⁻activity relationship study. Out of all structural features, the presence of hydroxyl group at the C7 and C18 residues, as well as their stereochemistry, were determined as important factors affecting the potential to disrupt the actin cytoskeleton. Moreover, reversibility of the actin disrupting effects was tested, revealing no direct correlations between potency and reversibility in the tested compound group. Since the diverse bioactivity of cytochalasans is interesting for various applications in eukaryotes, the exact effect on eukaryotic cells will need to be determined, e.g., by follow-up studies involving medicinal chemistry and by inclusion of additional natural cytochalasans. The results are also discussed in relation to previous studies in the literature, including a recent report on the anti-Biofilm activities of essentially the same panel of compounds against the pathogenic bacterium, Staphylococcus aureus.


Assuntos
Citoesqueleto de Actina/efeitos dos fármacos , Citocalasinas/química , Citocalasinas/farmacologia , Células Eucarióticas/efeitos dos fármacos , Citoesqueleto de Actina/metabolismo , Citocalasinas/isolamento & purificação , Células Eucarióticas/metabolismo , Humanos , Conformação Molecular , Relação Estrutura-Atividade , Células Tumorais Cultivadas
10.
Mar Drugs ; 17(2)2019 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-30781569

RESUMO

Three new eunicellin-derived diterpenoids of briarellin type, briarenones A‒C (1‒3), were isolated from a Formosan gorgonian Briareum violaceum. The chemical structures of the compounds were elucidated on the basis of extensive spectroscopic analyses, including two-dimensional (2D) NMR. The absolute configuration of 1 was further confirmed by a single crystal X-ray diffraction analysis. The in vitro cytotoxic and anti-inflammatory potentialities of the isolated metabolites were tested against the growth of a limited panel of cancer cell lines and against the production of superoxide anions and elastase release in N-formyl-methionyl-leucyl-phenyl-alanine and cytochalasin B (fMLF/CB)-stimulated human neutrophils, respectively.


Assuntos
Cnidários/química , Diterpenos/química , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Citocalasinas/farmacologia , Diterpenos/isolamento & purificação , Humanos , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Conformação Molecular , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Elastase Pancreática/metabolismo , Superóxidos/metabolismo , Difração de Raios X
11.
Org Lett ; 21(4): 1026-1030, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30730147

RESUMO

Amichalasines A-C (1-3), which represent a new type of cytochalasan heterotrimers, were isolated from Aspergillus micronesiensis PG-1. Compounds 1 and 2 possess an undecacyclic 5/6/11/5/5/6/6/5/11/6/5 ring system, and 3 has an additional furan ring with a dodecacyclic 5/6/11/5/5/6/6/5/5/11/6/5 ring system. 1 and 2 exhibited potent cytotoxic activities through apoptosis induction mediated by caspase-3 activation and PARP degradation, and their IC50 values against HL60 cells were 1.71 and 3.74 µM, respectively.


Assuntos
Antineoplásicos/farmacologia , Aspergillus/química , Citocalasinas/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Cristalografia por Raios X , Citocalasinas/química , Citocalasinas/isolamento & purificação , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Modelos Moleculares , Estrutura Molecular , Poli(ADP-Ribose) Polimerases/metabolismo , Relação Estrutura-Atividade
12.
Org Lett ; 21(4): 1108-1111, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30681869

RESUMO

Curtachalasins C-E (1-3), which have an unprecedent bridged 6/6/6/6 ring system, were identified from the endophytic fungus Xylaria cf. curta. Residual dipolar coupling analyses associating with density functional theory calculations were utilized to determine the relative configuration of noncrystallizable compound 2. The absolute configurations of 1-3 were determined by X-ray diffraction and electronic circular dichroism calculations. Remarkably, curtachalasin C (1) showed significant resistance reversal activity against fluconazole-resistant Candida albicans.


Assuntos
Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Citocalasinas/farmacologia , Farmacorresistência Fúngica/efeitos dos fármacos , Xylariales/química , Antifúngicos/química , Antifúngicos/isolamento & purificação , Cristalografia por Raios X , Citocalasinas/química , Citocalasinas/isolamento & purificação , Fluconazol/farmacologia , Testes de Sensibilidade Microbiana , Modelos Moleculares , Conformação Molecular
13.
Fitoterapia ; 132: 53-59, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30496809

RESUMO

Six new seco-cytochalasins A-F (1-6), two new asperlactones G-H (7-8) along with three known cytochalasins (9-11) were isolated from the solid cultures of an endophytic fungus Aspergillus sp. Their structures were elucidated by comprehensive spectral analysis, and their absolute configurations were determined through Mo2(OCOCH3)4-induced electronic circular dichroism (ECD) spectra and Rh2(OCOCF3)4-induced ECD experiment. Compounds 5 and 6 were rare seco-cytochalasins possessing an α, ß-unsaturated furanone structure in their side-chains. These isolates exhibited cytotoxicity against human lung cancer A-549 cell line with IC50 values ranging from 7.8 to 70.2 µM. At the concentration of 16 µM, compound 4 also exerted a 3-fold enhancement of doxorubicin susceptibility on doxorubicin-resistant human breast cancer (MCF-7/DOX) cell line.


Assuntos
Aspergillus/química , Citocalasinas/química , Pinellia/microbiologia , Tubérculos/microbiologia , Células A549 , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , China , Citocalasinas/isolamento & purificação , Endófitos/química , Humanos , Células MCF-7 , Estrutura Molecular
14.
Bioorg Chem ; 83: 98-104, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30343206

RESUMO

By feeding 1-methyl-l-tryptophan (1-MT) into cultures of the arthropod-associated fungus Chaetomium globosum TW1-1, three novel cytochalasan alkaloids, termed as armochaetoglosins A-C (1-3), together with five known analogues, namely prochaetoglobosin I (4), chaetoglobosin T (5), chaetoglobosin C (6), armochaetoglobin Y (7), and chaetoglobosin Vb (8), were isolated and characterized. Their structures including absolute configurations were elucidated by means of NMR spectroscopy, single-crystal X-ray crystallography, and comparison of the experimental electronic circular dichroism (ECD) spectra. Structurally, compounds 1-3 represented the first examples of 1'-N-methyl-chaetoglobosins, which were possibly biosynthesized from the additive 1-MT rather than tryptophan. Additionally, compound 3 showed the highest antibacterial activity against K. pneumoniae and ESBL-E. coli with MIC values of 4.0 µg/mL and 16.0 µg/mL, respectively, wherein the inhibitory effect of 3 against K. pneumoniae was stronger than that of the clinically used antibiotic meropenem, with an MIC value of 8 µg/mL. Our findings may provide new chemical templates for the development of new antibacterial agents against drug-resistant microbial pathogens.


Assuntos
Alcaloides/farmacologia , Antibacterianos/farmacologia , Chaetomium/química , Citocalasinas/farmacologia , Escherichia coli/efeitos dos fármacos , Klebsiella pneumoniae/efeitos dos fármacos , Alcaloides/química , Alcaloides/isolamento & purificação , Antibacterianos/química , Antibacterianos/isolamento & purificação , Cristalografia por Raios X , Citocalasinas/química , Citocalasinas/isolamento & purificação , Relação Dose-Resposta a Droga , Farmacorresistência Bacteriana/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Modelos Moleculares , Conformação Molecular , Relação Estrutura-Atividade
15.
Plant Biol (Stuttg) ; 21(2): 352-360, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30472775

RESUMO

This study aimed to examine the evidence of direct interaction among actin, myosin and phosphatidylinositol 3-kinase (PI3K) in the polarisation and formation of the tetraspore germ tube of Gelidium floridanum. After release, tetraspores were exposed to cytochalasin B, latrunculin B, LY294002 and BDM for a period of 6 h. In control samples, formation of the germ tube occurred after the experimental period, with cellulose formation and elongated chloroplasts moving through the tube region in the presence of F-actin. In the presence of cytochalasin B, an inhibitor of F-actin, latrunculin B, an inhibitor of G-actin, and BDM, a myosin inhibitor, tetraspores showed no formation of the germ tube or cellulose. Spherical-shaped chloroplasts were observed in the central region with a few F-actin filaments in the periphery of the cytoplasm. Tetraspores treated with LY294002, a PI3K inhibitor, showed no formation of the tube at the highest concentrations. Polarisation of cytoplasmic contents did not occur, only cellulose formation. It was concluded that F-actin directs the cell wall components and contributes to the maintenance of chloroplast shape and elongation during germ tube formation. PI3K plays a fundamental role in signalling for the asymmetric polarisation of F-actin. Thus, F-actin regulates the polarisation and germination processes of tetraspores of G. floridanum.


Assuntos
Citoesqueleto de Actina/metabolismo , Miosinas/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Rodófitas/metabolismo , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Parede Celular/metabolismo , Cloroplastos/metabolismo , Cromonas/farmacologia , Citocalasinas , Diacetil/análogos & derivados , Diacetil/farmacologia , Morfolinas/farmacologia , Inibidores de Fosfoinositídeo-3 Quinase , Estruturas Vegetais/crescimento & desenvolvimento , Estruturas Vegetais/metabolismo , Rodófitas/efeitos dos fármacos , Rodófitas/crescimento & desenvolvimento , Tiazolidinas/farmacologia
16.
Rapid Commun Mass Spectrom ; 33(1): 133-139, 2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30325552

RESUMO

RATIONALE: Microbial natural products are often biosynthesized as classes of structurally related compounds that have similar tandem mass spectrometry (MS/MS) fragmentation patterns. Mining MS/MS datasets for precursor ions that share diagnostic or common features enables entire chemical classes to be identified, including novel derivatives that have previously been unreported. Analytical data analysis tools that can facilitate a class-targeted approach to rapidly dereplicate known compounds and identify structural variants within complex matrices would be useful for the discovery of new natural products. METHODS: A diagnostic fragmentation filtering (DFF) module was developed for MZmine to enable the efficient screening of MS/MS datasets for class-specific product ions(s) and/or neutral loss(es). This approach was applied to series of the structurally related chaetoglobosin and cytochalasin classes of compounds. These were identified from the culture filtrates of three fungal genera: Chaetomium globosum, a putative new species of Penicillium (called here P. cf. discolor: closely related to P. discolor), and Xylaria sp. Extracts were subjected to LC/MS/MS analysis under positive electrospray ionization and operating in a data-dependent acquisition mode, performed using a Thermo Q-Exactive mass spectrometer. All MS/MS datasets were processed using the DFF module and screened for diagnostic product ions at m/z 130.0648 and 185.0704 for chaetoglobosins, and m/z 120.0808 and 146.0598 for cytochalasins. RESULTS: Extracts of C. globosum and P. cf. discolor strains revealed different mixtures of chaetoglobosins, whereas the Xylaria sp. produced only cytochalasins; none of the strains studied produced both classes of compounds. The dominant chaetoglobosins produced by both C. globosum and P. cf. discolor were chaetoglobosins A, C, and F. Tetrahydrochaetoglobosin A was identified from P. cf. discolor extracts and is reported here for the first time as a natural product. The major cytochalasins produced by the Xylaria sp. were cytochalasin D and epoxy cytochalasin D. A larger unknown "cytochalasin-like" molecule with the molecular formula C38 H47 NO10 was detected from Xylaria sp. culture filtrate extracts and is a current target for isolation and structural characterization. CONCLUSIONS: DFF is an effective LC/MS data analysis approach for rapidly identifying entire classes of compounds from complex mixtures. DFF has proved useful in the identification of new natural products and allowing for their partial characterization without the need for isolation.


Assuntos
Citocalasinas/química , Descoberta de Drogas/métodos , Alcaloides Indólicos/química , Software , Espectrometria de Massas em Tandem/métodos , Chaetomium/química , Chaetomium/metabolismo , Cromatografia Líquida , Citocalasinas/análise , Avaliação Pré-Clínica de Medicamentos/métodos , Fermentação , Alcaloides Indólicos/análise , Metabolômica/métodos , Penicillium/química , Penicillium/metabolismo , Xylariales/química , Xylariales/metabolismo
17.
Plant Cell ; 31(1): 189-209, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30563847

RESUMO

Hypersensitive response (HR) cell death is the most effective plant immune response restricting fungal pathogen invasion. Here, we report that incompatible rice (Oryza sativa) Magnaporthe oryzae interactions induce iron- and reactive oxygen species (ROS)-dependent ferroptotic cell death in rice cells. Ferric ions and ROS (i.e., H2O2) accumulated in tissues undergoing HR cell death of rice leaf sheath tissues during avirulent M. oryzae infection. By contrast, iron did not accumulate in rice cells during virulent M. oryzae infection or treatment with the fungal elicitor chitin. Avirulent M. oryzae infection in ΔOs-nadp-me2-3 mutant rice did not trigger iron and ROS accumulation and suppressed HR cell death, suggesting that NADP-malic enzyme2 is required for ferroptotic cell death in rice. The small-molecule ferroptosis inhibitors deferoxamine, ferrostatin-1, and cytochalasin E and the NADPH oxidase inhibitor diphenyleneiodonium suppressed iron-dependent ROS accumulation and lipid peroxidation to completely attenuate HR cell death in rice sheaths during avirulent M. oryzae infection. By contrast, the small-molecule inducer erastin triggered iron-dependent ROS accumulation and glutathione depletion, which ultimately led to HR cell death in rice in response to virulent M. oryzae These combined results demonstrate that iron- and ROS-dependent signaling cascades are involved in the ferroptotic cell death pathway in rice to disrupt M. oryzae infection.


Assuntos
Ferro/metabolismo , Magnaporthe/patogenicidade , Oryza/metabolismo , Oryza/microbiologia , Espécies Reativas de Oxigênio/metabolismo , Cicloexilaminas/farmacologia , Citocalasinas/farmacologia , Desferroxamina/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Fenilenodiaminas/farmacologia
18.
Org Lett ; 20(24): 7758-7761, 2018 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-30499682

RESUMO

Two unique cytochalasans, curtachalasins A (1) and B (2), were purified from the endophytic fungus Xylaria curta E10 harbored in the plant Solanum tuberosum. Their structures were determined by extensive spectroscopic methods, X-ray crystallographic analysis, and electronic circular dichroism calculations. These two compounds feature an unprecedented pyrolidine/perhydroanthracene (5/6/6/6 tetracyclic skeleton) fused ring system.


Assuntos
Citocalasinas/isolamento & purificação , Xylariales/química , Cristalografia por Raios X , Citocalasinas/química , Modelos Moleculares , Estrutura Molecular , Rhabdoviridae/química , Estereoisomerismo
19.
J Asian Nat Prod Res ; 20(10): 1002-1007, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30415573

RESUMO

A new cytochalasin derivative xylarisin B (1), together with four known compounds astropyrone (2), guaidiol (3), xylaropyrone B (4), and xylaropyrone C (5), were isolated from the fermentation broth of Xylaria sp. HNWSW-2. Their structures were elucidated by spectroscopic data. Among them, compounds 2 and 3 at a concentration of 50 µg/ml showed weak inhibitory activity against AChE with inhibition rates of 10.4 and 12.9%, respectively. In addition, compound 2 also exhibited inhibitory activity against α-glycosidase with inhibition rate of 77.0% at a concentration of 0.25 mg/ml.


Assuntos
Citocalasinas/isolamento & purificação , Endófitos/química , Xylariales/química , Inibidores da Colinesterase/farmacologia , Citocalasinas/química , Citocalasinas/farmacologia , Fermentação , Inibidores de Glicosídeo Hidrolases/farmacologia , Espectroscopia de Ressonância Magnética
20.
Chemistry ; 24(62): 16686-16691, 2018 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-30168631

RESUMO

An intramolecular Diels-Alder (IMDA) reaction efficiently accelerated by Schreiner's thiourea is reported, to build a functionalized cytochalasin scaffold (periconiasin series) for biological purposes. DFT calculation highlighted a unique multidentate cooperative hydrogen bonding in this catalysis. The deprotection end game afforded a collection of diverse structures and showed the peculiar reactivity of the Diels-Alder cycloadducts upon functionalization. Biological studies revealed strong cytotoxicity of a few compounds on breast cancer cell lines while actin polymerization is preserved.


Assuntos
Antineoplásicos/química , Citocalasinas/química , Citoesqueleto de Actina/efeitos dos fármacos , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Catálise , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cobre/química , Cristalografia por Raios X , Reação de Cicloadição , Citocalasinas/síntese química , Citocalasinas/farmacologia , Humanos , Ligação de Hidrogênio , Conformação Molecular , Paládio/química , Estereoisomerismo , Termodinâmica , Tioureia/química
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