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1.
J Agric Food Chem ; 68(1): 185-192, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31815467

RESUMO

Phytopathogenic fungi have been considered as being an enormous threat in the agricultural system. In our search of new antifungal natural products, nine new halogenated cyclopentenones, bicolorins A-I (1-3, and 5-10), along with three known cyclopentenones (4, 11, and 12) were isolated from the endophytic fungus Saccharicola bicolor of Bergenia purpurascens by the one strain-many compounds strategy. Their structures and absolute configurations were elucidated based on extensive spectroscopic analysis, X-ray crystallographic analysis, and time-dependent density functional theory-equivalent circulating density calculations. Compounds 1-12 showed antifungal activities against five phytopathogenic fungi (Uromyces viciae-fabae, Pythium dissimile, Gibberella zeae, Aspergillus niger, and Sclerotinia sclerotiorum). Especially, bicolorins B and D (2 and 5) exhibited strong antifungal activities against P. dissimile with the MIC values of 6.2 and 8.5 µg/mL, respectively, compared with the positive control cycloheximide (MIC of 8.6 µg/mL). Additionally, bicolorin D was proven to be potently antifungal against S. sclerotiorum in vitro and in vivo. This work provides an effective strategy for searching antifungal candidate agents.


Assuntos
Ascomicetos/química , Ciclopentanos/química , Ciclopentanos/farmacologia , Endófitos/química , Fungicidas Industriais/química , Fungicidas Industriais/farmacologia , Saxifragaceae/microbiologia , Ascomicetos/isolamento & purificação , Ascomicetos/metabolismo , Ciclopentanos/metabolismo , Endófitos/isolamento & purificação , Endófitos/metabolismo , Fungos/efeitos dos fármacos , Fungos/crescimento & desenvolvimento , Fungicidas Industriais/metabolismo , Halogenação , Estrutura Molecular , Doenças das Plantas/microbiologia
2.
Zhongguo Zhong Yao Za Zhi ; 44(18): 4021-4025, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31872740

RESUMO

Phytochemical investigation of the culture of Epicoccum nigrum,an endolichenic fungus inhabiting Leptogium masiaticum,led to the isolation of 11 compounds. Based on NMR spectroscopy and HRESIMS data,their structures were determined as one alkaloid fusaricide( 1),and seven benzofuran derivatives including epicoccone( 2),4,6-dihydroxy-5-methoxy-7-methyl-1,3-dihydro isobenzofuran( 3),5-methyl-epicoccone B( 4),3,6,7-trihydroxy-5-methoxy-4-methylisobenzo furan-1( 3 H)-one( 5),3-methoxyepicoccone B( 6),2,3,4-trihydroxy-6-( hydroxymethyl)-5-methylbenzyl-alcohol( 7),and isoochracinic acid( 8),together with three epicoccolide analogs epicocconigrones A( 9),epicoccolide B( 10),and epicocconigrones B( 11). Compounds 1,9 and 10 showed potent microorganism inhibitory effects. These results indicated the potential perspective of this endophytic fungus as an eco-friendly biocide.


Assuntos
Ascomicetos/química , Endófitos/química , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Metabolismo Secundário
3.
Org Biomol Chem ; 17(47): 10009-10012, 2019 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-31755515

RESUMO

Two novel polyketones, rhizophols A-B (1-2), were isolated from the endophytic fungus Cytospora rhizophorae A761. They shared unprecedented poly-substituted benzophenone skeletons featuring an epoxy isopentyl unit and a propionyl moiety. Their structures were evidenced by extensive spectroscopic analyses, X-ray diffraction, and quantum energy calculation. Moreover, compound 1 was proved to be a promising lead compound for novel antioxidant drugs.


Assuntos
Antioxidantes/farmacologia , Ascomicetos/química , Benzofenonas/farmacologia , Compostos de Bifenilo/antagonistas & inibidores , Picratos/antagonistas & inibidores , Antioxidantes/síntese química , Antioxidantes/química , Benzofenonas/síntese química , Benzofenonas/química , Cristalografia por Raios X , Modelos Moleculares , Conformação Molecular , Teoria Quântica
4.
J Agric Food Chem ; 67(47): 13040-13050, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31670962

RESUMO

Two new natural 10-membered macrolides (1, 2) and one chromene-4,5-dione derivative (3), named stagonolides J and K and stagochromene A, respectively, were isolated from the phytopathogenic fungus Stagonospora cirsii S-47, together with two known compounds, stagonolide A (4) and herbarumin I (5). Stagonolides J and K and stagochromene A were characterized as (5E,7R*,8S*,9R*)-7,8-dihydroxy-9-propyl-5-nonen-9-olide, (5E,7R,9S)-7-hydroxy-9-propyl-5-nonen-9-olide, and (2R*,3R*)-3-hydroxy-2-propyltetrahydro-2H-chromene-4,5(3H,4aH)-dione, respectively, by spectroscopic (mostly by NMR and ESIMS) data. Compounds 1-5 showed different rates of phytotoxic activity on punctured leaf discs of Sonchus arvensis. The antimicrobial, cytotoxic, and antiprotozoal activity of isolated compounds was also evaluated. Based on our data, stagonolide K and herbarumin I can be proposed as a potential scaffold for the development of a new natural herbicide and estimated as possible selection/quality markers of a bioherbicide based on S. cirsii, while stagonolide A can be considered as a mycotoxin.


Assuntos
Ascomicetos/química , Benzopiranos/química , Herbicidas/química , Compostos Heterocíclicos com 1 Anel/química , Lactonas/química , Macrolídeos/química , Sonchus/efeitos dos fármacos , Benzopiranos/farmacologia , Herbicidas/farmacologia , Compostos Heterocíclicos com 1 Anel/farmacologia , Lactonas/farmacologia , Macrolídeos/farmacologia , Estrutura Molecular , Micotoxinas/química , Micotoxinas/farmacologia , Sonchus/crescimento & desenvolvimento
5.
J Agric Food Chem ; 67(47): 13185-13194, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31697490

RESUMO

In searching for novel fungicidal leads, the novel bioactive succinate dehydrogenase inhibitor (SDHI) derivatives were designed and synthesized by the inversion of carbonyl and amide groups. Bioassay indicated that compound 5i stood out with a broad spectrum of in vitro activity against five fungi. Its EC50 value (0.73 µg/mL) was comparable to that of boscalid (EC50 of 0.51 µg/mL) and fluxapyroxad (EC50 of 0.19 µg/mL) against Sclerotinia sclerotiorum. For Rhizoctonia cerealis, 5i and 5p with EC50 values of 4.61 and 6.48 µg/mL, respectively, showed significantly higher activity than fluxapyroxad with the EC50 value of 16.99 µg/mL. In vivo fungicidal activity of 5i exhibited an excellent inhibitory rate (100%) against Puccinia sorghi at 50 µg/mL, while the positive control boscalid showed only a 70% inhibitory rate. Moreover, 5i showed promising fungicidal activity with a 60% inhibitory rate against Rhizoctonia solani at 1 µg/mL, which was better than that of boscalid (30%). Compound 5i possessed better in vivo efficacy against P. sorghi and R. solani than boscalid. Molecular docking showed that even the carbonyl oxygen atom of 5i was far from the pyrazole ring. It could also form hydrogen bonds toward the hydroxyl hydrogen and amino hydrogen of TYR58 and TRP173 on SDH, respectively, which consisted of the positive control fluxapyroxad. Fluorescence quenching analysis and SDH enzymatic inhibition studies also validated its mode of action. Our studies showed that 5i was worthy of further investigation as a promising fungicide candidate.


Assuntos
Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Proteínas Fúngicas/antagonistas & inibidores , Fungicidas Industriais/síntese química , Fungicidas Industriais/farmacologia , Succinato Desidrogenase/antagonistas & inibidores , Ascomicetos/química , Ascomicetos/efeitos dos fármacos , Ascomicetos/enzimologia , Inibidores Enzimáticos/química , Proteínas Fúngicas/química , Proteínas Fúngicas/metabolismo , Fungicidas Industriais/química , Simulação de Acoplamento Molecular , Rhizoctonia/química , Rhizoctonia/efeitos dos fármacos , Rhizoctonia/enzimologia , Relação Estrutura-Atividade , Succinato Desidrogenase/química , Succinato Desidrogenase/metabolismo
6.
J Agric Food Chem ; 67(47): 13061-13072, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31738551

RESUMO

In this study, we purified three new sesquiterpenyl epoxy-cyclohexenoid (SEC) analogues, arthrobotrisin D (11) and its two derivatives, from nematode-trapping fungus Arthrobotrys oligospora. Our results revealed that arthrobotrisin type SEC metabolites could be detected in all the test fungal strains from geographically distinct regions grown on different nutrient media, indicative of unique diagnostic character as chemical indicators for A. oligospora. The time course designs over short-term intervals of the fungus under direct contact and indirect contact with living or dead nematodes revealed that arthrobotrisin B and D (6 and 11) displayed significant relationships (positive or negative correlation) with fungal saprophytic and pathogenic stages during a nematode predation event. Interestingly, fungus on nutrient-limiting medium conducive to fungal trap formation could rapidly drop the concentration levels of arthrobotrisins B and D within 6 h when dead nematodes were around, in great contrast to that for living nematodes. Moreover, only in the fungal strain under direct contact with living dominant soil bacteria, arthrobotrisins B and D exhibited significant increase in amounts. Among them, the new SEC, arthrobotrisin D (11) was found to be a key unique metabolic signal for fungal colony growth and fungal interaction with prey and bacteria. Our study suggested that chemical analysis of SEC metabolites in A. oligospora provides a window into the fungal growth status and much valuable information about ecological environments associated with the nematode infections.


Assuntos
Ascomicetos/química , Compostos de Epóxi/química , Nematoides/microbiologia , Sesquiterpenos/química , Animais , Ascomicetos/crescimento & desenvolvimento , Ascomicetos/metabolismo , Compostos de Epóxi/metabolismo , Estrutura Molecular , Sesquiterpenos/metabolismo
7.
Fitoterapia ; 139: 104369, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31626911

RESUMO

Five new polyketides, colletotric B (2), 3-hydroxy-5-methoxy-2,4,6-trimethylbenzoic acid (3), colletotric C (4), chaetochromone D (6) and 8-hydroxy-pregaliellalactone B (9), together with four known analogues (1, 5 and 7-8) were isolated from the mangrove endophytic fungus Phoma sp. SYSU-SK-7. Their structures were elucidated by analysis of extensive spectroscopic data and mass spectrometric data. Compounds 1-2 showed strong antimicrobial activity against the P. aeruginosa, MRSA and C. albicans with the MIC values in the range of 1.67-6.28 µg/ml. Furthermore, Compounds 1-5 also exhibited significant α-glucosidase inhibitory activity with the IC50 values in the range of 36.2-90.6 µM. Compound 7 was found to inhibited radical scavenging activity against DPPH with the EC50 value of 11.8 µM.


Assuntos
Anti-Infecciosos/farmacologia , Ascomicetos/química , Depuradores de Radicais Livres/farmacologia , Inibidores de Glicosídeo Hidrolases/farmacologia , Policetídeos/farmacologia , Rhizophoraceae/microbiologia , Anti-Infecciosos/isolamento & purificação , China , Endófitos/química , Depuradores de Radicais Livres/isolamento & purificação , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Testes de Sensibilidade Microbiana , Estrutura Molecular , Policetídeos/isolamento & purificação
8.
Chem Biodivers ; 16(12): e1900519, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31596057

RESUMO

A new pimarane diterpenoid, named botryopimarene A (1), was discovered from the fungus Botryotinia fuckeliana MCCC 3 A00494 isolated from the deep-sea water, together with ten known compounds. The planar structure of 1 was established based on the extensive spectroscopic analyses. The absolute configurations of tricyclic system in 1 were resolved by the theoretical ECD calculation, while the 15,16-diol moiety in the side chain was resolved by the Mo2 (OAc)4 -induced ECD spectrum. Compound 1, featuring a Δ9(11) double bond, was rarely discovered in pimarane family. Compounds 1-11 were tested for their cytotoxic activities using six human cancer cell lines by the MTT method. However, none of the compounds exhibited detectable cytotoxicities (IC50 >20 µm).


Assuntos
/química , Ascomicetos/química , Diterpenos/química , Água do Mar/microbiologia , /isolamento & purificação , Ascomicetos/isolamento & purificação , Ascomicetos/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Dicroísmo Circular , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Humanos , Conformação Molecular
9.
Zhongguo Zhong Yao Za Zhi ; 44(15): 3213-3220, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602874

RESUMO

A total of 27 endophytic fungal strains were isolated from Huperzia serrata,which were richly distributed in the stems and leaves while less distributed in roots. The 27 strains were identified by Internal Transcribed Spacer( ITS) r DNA molecular method and one of the strains belongs to Basidiomycota phylum,and other 26 stains belong to 26 species,9 general,6 families,5 orders,3 classes of Ascomycota Phylum. The dominant strains were Colletotrichum genus,belonging to Glomerellaceae family,Glomerellales order,Sordariomycetes class,Ascomycota Phylum,with the percentage of 48. 15%. The inhibitory activities of the crude extracts of 27 endophytic fungal strains against acetylcholinesterase( ACh E) and nitric oxide( NO) production were evaluated by Ellman's method and Griess method,respectively. Crude extracts of four fungi exhibited inhibitory activities against ACh E with an IC50 value of 42. 5-62. 4 mg·L~(-1),and some fungi's crude extracts were found to inhibit nitric oxide( NO) production in lipopolysaccharide( LPS)-activated RAW264. 7 macrophage cells with an IC50 value of 2. 2-51. 3 mg·L~(-1),which indicated that these fungi had potential anti-inflammatory activities.The chemical composition of the Et OAc extract of endophytic fungus HS21 was also analyzed by LCMS-IT-TOF. Seventeen compounds including six polyketides,four diphenyl ether derivatives and seven meroterpenoids were putatively identified.


Assuntos
Ascomicetos/química , Ascomicetos/classificação , Huperzia/microbiologia , Acetilcolinesterase , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Ascomicetos/isolamento & purificação , Inibidores da Colinesterase/isolamento & purificação , Inibidores da Colinesterase/metabolismo , Endófitos/classificação , Endófitos/isolamento & purificação , Camundongos , Células RAW 264.7
10.
Fitoterapia ; 139: 104390, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31655088

RESUMO

From extracts of the plant associated fungus Chaetosphaeronema achilleae collected in Iran, a previously unreported isoindolinone named chaetosisoindolinone (1) and a previously undescribed indanone named chaetosindanone (2) were isolated in addition to five known metabolites, 2-(2-acetyl-3,5-dihydroxyphenyl) acetic acid (3), vulculic acid (4), 2-(2-acetyl-3-hydroxy-5-methoxyphenyl)acetic acid (5), curvulin (6), and curvulol (7). Their structures were elucidated on the basis of extensive spectroscopic analysis and high-resolution mass spectrometry. The isolated compounds were tested for their antimicrobial, anti-biofilm, and nematicidal activities. Compound 2 exhibited cytotoxicity against the human breast adenocarcinoma MCF-7 cells with an IC50 value of 1.5 µg/mL. Furthermore, compounds 4 and 7 almost completely inhibited biofilm formation in Staphylococcus aureus at 256 µg/mL. Weak antimicrobial activities were also observed for some of the isolated compounds against Mucor hiemalis, Rhodoturula glutinis, Chromobacterium violaceum, and Staphylococcus aureus.


Assuntos
Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Ascomicetos/química , Biofilmes/efeitos dos fármacos , Taxus/microbiologia , Antibacterianos/isolamento & purificação , Antineoplásicos/isolamento & purificação , Humanos , Irã (Geográfico) , Células MCF-7 , Testes de Sensibilidade Microbiana , Estrutura Molecular , Staphylococcus aureus/efeitos dos fármacos
11.
Oxid Med Cell Longev ; 2019: 6029876, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31396303

RESUMO

This study investigated the hepatoprotective effects of Morchella esculenta fruit body (ME) and the underlying mechanisms in mice with alcohol-induced acute liver injury. Systematic analysis revealed that ME contained 21 types of fatty acid, 17 types of amino acid, and 12 types of mineral. Subsequently, a mouse model of acute alcohol-induced liver injury was established by oral administration of alcohol for 14 days. Fourteen-day administration of ME prevented alcohol-induced increases in alanine aminotransferase and aspartate aminotransferase levels and reduced the activity of acetaldehyde dehydrogenase in blood serum and liver tissue. ME appears to regulate lipid metabolism by suppressing triglycerides, total cholesterol, and high-density lipoprotein in the liver. ME inhibited the production of inflammatory factors including chitinase-3-like protein 1 (YKL 40), interleukin-7 (IL-7), plasminogen activator inhibitor type 1 (PAI-1), and retinol-binding protein 4 (RBP4) in blood serum and/or liver tissue. ME treatment relieved the alcohol-induced imbalance in prooxidative and antioxidative signaling via nuclear factor-erythroid 2-related factor 2 (Nrf-2), as indicated by upregulation of superoxide dismutase-1, superoxide dismutase-2, catalase, heme oxygenase-1, and heme oxygenase-2 expression and downregulation of kelch-like ECH-associated protein 1 (Keap-1) in the liver. Moreover, ME reduced the levels of phosphorylated nuclear factor kappa-B kinase α/ß, inhibitor of nuclear factor kappa-B α and nuclear factor kappa-B p65 (NF-κB p65) in the liver. The hepatoprotective effects of ME against alcohol-induced acute liver injury were thus confirmed. The mechanism of action may be related to modulation of antioxidative and anti-inflammatory signaling pathways, partially via regulation of Nrf-2 and NF-κB signaling.


Assuntos
Ascomicetos/química , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Substâncias Protetoras/farmacologia , Transdução de Sinais/efeitos dos fármacos , Alanina Transaminase/sangue , Animais , Antioxidantes/metabolismo , Ascomicetos/metabolismo , Aspartato Aminotransferases/sangue , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/veterinária , Etanol/toxicidade , Heme Oxigenase-1/metabolismo , Mediadores da Inflamação/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Rim/metabolismo , Rim/patologia , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos
12.
Molecules ; 24(15)2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31370299

RESUMO

Radicinin (1), is a fungal dihydropyranopyran-4,5-dione isolated together with some analogues, namely 3-epi-radicinin, radicinol, 3-epi-radicinol, and cochliotoxin (2-5), from the culture filtrates of the fungus Cochliobolus australiensis, a foliar pathogen of buffelgrass (Cenchrus ciliaris), an invasive weed in North America. Among the different metabolites 1 showed target-specific activity against the host plant and no toxicity on zebrafish embryos, promoting its potential use to develop a natural bioherbicide formulation to manage buffelgrass. These data and the peculiar structural feature of 1 suggested to carry out a structure-activity relationship study, preparing some key hemisynthetic derivatives and to test their phytotoxicity. In particular, p-bromobenzoyl, 5-azidopentanoyl, stearoyl, mesyl and acetyl esters of radicinin were semisynthesized as well as the monoacetyl ester of 3-epi-radicinin, the diacetyl esters of radicinol and its 3 epimer, and two hexa-hydro derivatives of radicinin. The spectroscopic characterization and the activity by leaf puncture bioassay against buffelgrass of all the derivatives is reported. Most of the compounds showed phytotoxicity but none of them had comparable or higher activity than radicinin. Thus, the presence of an α,ß unsaturated carbonyl group at C-4, as well as, the presence of a free secondary hydroxyl group at C-3 and the stereochemistry of the same carbon proved to be the essential feature for activity.


Assuntos
Cenchrus/efeitos dos fármacos , Plantas Daninhas/efeitos dos fármacos , Pironas/química , Relação Estrutura-Atividade , Alcaloides/química , Alcaloides/farmacologia , Ascomicetos/química , Cenchrus/crescimento & desenvolvimento , Fungos Mitospóricos/química , Estrutura Molecular , América do Norte , Plantas Daninhas/crescimento & desenvolvimento , Pironas/farmacologia , Toxinas Biológicas/química , Toxinas Biológicas/farmacologia
13.
BMC Complement Altern Med ; 19(1): 221, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31426865

RESUMO

BACKGROUND: Lichens produce a huge diversity of bioactive compounds with several biological effects. Gyrophoric acid (GA) is found in high concentrations in the common lichen Umbilicaria hirsuta, however evidence for biological activity was limited to anti-proliferative activity described on several cancer cell lines. METHODS: We developed and validated a new protocol for GA isolation, resulting in a high yield of highly pure GA (validated by HPLC and NMR) in an easy and time saving manner. Anti-proliferative and pro-apoptotic activity, oxygen radicals formation and stress/survival proteins activity changes was study by flow cytometry. RESULTS: The highly purified GA showed anti-proliferative activity against HeLa (human cervix carcinoma) and other tumor cells. Moreover, GA threated cells showed a significant increase in caspase-3 activation followed by PARP cleavage, PS externalization and cell cycle changes mediated by oxidative stress. Production of oxygen radicals led to DNA damage and changes in stress/survival pathways activation. CONCLUSIONS: GA treatment on HeLa cells clearly indicates ROS production and apoptosis as form of occurred cell death. Moreover, DNA damage and changing activity of stress/survival proteins as p38MAPK, Erk1/2 and Akt mediated by GA treatment confirm pro-apoptotic potential. The pharmacological potential of U. hirsuta derived GA is discussed.


Assuntos
Apoptose/efeitos dos fármacos , Benzoatos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Líquens/química , Estresse Oxidativo/efeitos dos fármacos , Ascomicetos/química , Células HeLa , Humanos , Transdução de Sinais/efeitos dos fármacos
14.
Chem Biol Interact ; 311: 108798, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31433962

RESUMO

Natural products are a valuable source of anticancer agents, with many naturally derived compounds currently used in clinical and preclinical treatments. This study aims to investigate the antiproliferative activity and potential mechanism of action of the xanthoquinodin JBIR-99, isolated from fungi Parengyodontium album MEXU 30,054 and identified by single-crystal X-ray crystallography. Cytotoxicity of xanthoquinodin was evaluated in a panel of human cancer cells lines and CCD-112-CoN normal colon cells, using the sulforhodamine B assay. PC-3 prostate cancer cells were used in biochemical assays including cell cycle, mitochondrial transmembrane potential (MTP), reactive oxygen species (ROS) and caspase activity. Expression levels of apoptosis-pathway-related proteins were analyzed by Western blot. The in vivo toxicity of xanthoquinodin was determined using a zebrafish model. Xanthoquinodin showed cytotoxicity in all cancer cell lines but demonstrated relative selective potency against PC-3 cells with an IC50 1.7 µM. In CCD-112-CoN cells, xanthoquinodin was non-cytotoxic at 100 µM. In PC-3 cells, the compound induced loss of MTP, production of ROS, and cell cycle arrest in S phase. The expression and activity of caspase-3 was increased, which correlates with the upregulation of Cyt c, Bax, nuclear factor kappa-B (NF-κB) (p65) and IKKß, and downregulation of poly ADP ribose polymerase (PARP-1) and Bcl-2. Lastly, xanthoquinodin did not cause any visible developmental toxicity in zebrafish at 50 µM. These results demonstrate xanthoquinodin induces apoptosis in PC-3 prostate cancer cells by activation of both intrinsic and extrinsic apoptotic pathways. In addition, the non-toxic effect in vivo indicates that xanthoquinodin could be a useful lead in the development of a novel, anti-cancer agent that is selective for prostate cancer.


Assuntos
Apoptose/efeitos dos fármacos , Ascomicetos/química , Cromonas/farmacologia , Ascomicetos/metabolismo , Linhagem Celular Tumoral , Cromonas/química , Cristalografia por Raios X , Citocromos c/metabolismo , Humanos , Quinase I-kappa B/metabolismo , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Conformação Molecular , Poli(ADP-Ribose) Polimerase-1/metabolismo , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteínas Repressoras/metabolismo , Pontos de Checagem da Fase S do Ciclo Celular/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
15.
Mar Drugs ; 17(8)2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31434338

RESUMO

Four new metabolites, asperchalasine I (1), dibefurin B (2) and two epicoccine derivatives (3 and 4), together with seven known compounds (5-11) were isolated from a mangrove fungus Mycosphaerella sp. SYSU-DZG01. The structures of compounds 1-4 were established from extensive spectroscopic data and HRESIMS analysis. The absolute configuration of 1 was deduced by comparison of ECD data with that of a known structure. The stereostructures of 2-4 were further confirmed by single-crystal X-ray diffraction. Compounds 1, 8 and 9 exhibited significant α-glucosidase inhibitory activity with IC50 values of 17.1, 26.7 and 15.7 µM, respectively. Compounds 1, 4, 6 and 8 showed antioxidant activity by scavenging DPPH· with EC50 values ranging from 16.3 to 85.8 µM.


Assuntos
Antioxidantes/química , Ascomicetos/química , Ascomicetos/metabolismo , Inibidores de Glicosídeo Hidrolases/química , Cristalografia por Raios X , Estrutura Molecular , alfa-Glucosidases/metabolismo
16.
J Agric Food Chem ; 67(37): 10505-10512, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31462045

RESUMO

An aspartic protease gene (Bsapa) was cloned from Bispora sp. MEY-1 and expressed in Pichia pastoris. The recombinant BsAPA showed maximal activity at pH 3.0 and 75 °C and remained stable at 70 °C and below, indicating the thermostable nature of BsAPA. However, heat inactivation still limits the application of BsAPA. To further improve its thermostability, an autocatalysis site (L205-F206) in BsAPA was identified and three mutants (F193W, K204P, and A371V) were generated based on the analysis of the structure neighboring the autocatalysis site. These mutants have improved thermostability, and their half-life at 75 °C increased by 0.5-, 0.2-, and 0.3-fold, respectively. A triple-site mutant (F193W/K204P/A371V) was generated, with 1.5-fold increased half-life at 80 and a 10.7 °C increased Tm, compared with those of the wild-type. These results indicate that autocatalysis of aspartic protease reduces enzyme thermostability. Furthermore, site-directed mutagenesis at regions near the autocatalysis site is an efficient approach to improve aspartic protease thermostability.


Assuntos
Ascomicetos/enzimologia , Ácido Aspártico Proteases/química , Ácido Aspártico Proteases/genética , Proteínas Fúngicas/química , Proteínas Fúngicas/genética , Ascomicetos/química , Ascomicetos/genética , Ácido Aspártico Proteases/metabolismo , Estabilidade Enzimática , Proteínas Fúngicas/metabolismo , Temperatura Alta , Cinética , Mutagênese Sítio-Dirigida , Mutação , Pichia/genética , Pichia/metabolismo
17.
Zhongguo Zhong Yao Za Zhi ; 44(9): 1889-1894, 2019 May.
Artigo em Chinês | MEDLINE | ID: mdl-31342718

RESUMO

To search for the active diuretic fractions of Clematidis Armandii Caulis( CAC) and determine its main active chemical components by using liquid chromatography-mass spectrometry( LC-MS) and diuretic activity evaluation. CAC 75% ethanol extracts and extracts from different polar solvents were orally administered to saline-loaded rats at different doses. 6 h urinary volume,p H and contents of electrolyte Na+,K+and Cl-were measured. The chemical components of the active fractions were separated and identified by ultra performance liquid chromatography-electrospray ionization-quadrupole time of flight-mass spectrometry( UPLC-ESI-Q-TOF-MS/MS) method. As compared with the control group,the urine volume was increased by 44%( P< 0. 01) and 34%( P < 0. 05) in CAC75% ethanol extract 57. 74 and 28. 8 mg·kg-1 groups respectively; the Na+excretion was increased by 52%( P< 0. 01) and 45%( P<0. 05),respectively; while the Cl-excretion was increased by 101%( P<0. 01) and 85%( P<0. 05),respectively. The urine volume,Na+excretion and Cl-excretion were increased by 50%( P< 0. 01),58%( P< 0. 05),and 65%( P< 0. 05) respectively in petroleum ether extract 70. 98 mg·kg-1 group as compared with the control group. While for the n-butanol extract 194. 18 mg·kg-1 group,the urine volume,Na+and Cl-excretion were increased by 42%( P<0. 01),41%( P<0. 05) and 97%( P<0. 01),respectively. The diuretic activity of other fractions was not obvious. There was no statistical difference in K+excretion in all groups. The results of LC-MS analysis showed that six compounds,including two sterols,one chromogen and three fatty acids,were identified from petroleum ether extract.Fourteen compounds,including six triterpenoid saponins,six lignin glycosides,one sterol glycoside and one phenolic glycoside,were identified from the n-butanol extract. All the results suggested that the ethanol extract of CAC had remarkable diuretic activity and its main effective components included sterol,triterpenoid saponin and lignin glycosides.


Assuntos
Ascomicetos/química , Diuréticos/farmacologia , Materia Medica/farmacologia , Animais , Ratos , Solventes , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem
18.
Mar Drugs ; 17(8)2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31344982

RESUMO

Advances in whole-genome sequencing of many fungal species has revealed the presence of numerous "silent" biosynthetic genes, highlighting their potential to produce a wide variety of natural products. These silent biosynthetic genes are regulated in part by their highly condensed chromatin structure, which can be modified to allow transcription in response to external stimuli. In this study, Asteromyces cruciatus was subjected to both epigenetic modification and osmotic stress to enhance the production of new natural products. This "cooperative induction" strategy led to the isolation and characterization of two new polyketides from a fermentation of A. cruciatus treated with suberoylanilide hydroxamic acid and sodium chloride. The metabolic profiles of the control and treated samples were assessed using ultra-high performance liquid chromatography high-resolution electrospray ionization mass spectrometry (UHPLC-HRESIMS) metabolomic analysis, highlighting the upregulation of two new polyketides, primarolides A and B. These compounds were purified using reversed-phase flash chromatography followed by high-performance liquid chromatography, and their planar structures were established using NMR spectroscopy.


Assuntos
Organismos Aquáticos/química , Ascomicetos/química , Ascomicetos/efeitos dos fármacos , Produtos Biológicos/química , Ácidos Hidroxâmicos/farmacologia , Osmose/fisiologia , Policetídeos/química , Ascomicetos/fisiologia , Cromatografia Líquida de Alta Pressão/métodos , Espectroscopia de Ressonância Magnética/métodos , Espectrometria de Massas/métodos , Cloreto de Sódio/farmacologia
19.
World J Microbiol Biotechnol ; 35(7): 108, 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31267227

RESUMO

A total of 191 yeasts were isolated from 197 samples collected from eight estuarine mangrove forests along four different coastlines of Thailand (Andaman Sea and the East, North and West coasts of the Gulf of Thailand). Of these, 178 isolates were identified as 32 species in 16 genera of Ascomycota, 12 species in nine genera of Basidiomycota, and 13 isolates as potential new species, respectively. Mangroves located along the Andaman Sea coastline had a higher yeast diversity at the species and genera levels than those along the Gulf of Thailand. Kluyveromyces siamensis was the most frequently isolated species, whilst Candida tropicalis was the only species isolated at all eight sites. Screening isolated yeast strains belonging to genera previously reported as oleaginous yeast plus the 13 potential new species, revealed two oleaginous strains, Rhodotorula sphaerocarpa 11-14.4 and Saitozyma podzolica 11-11.3.1. Both of these strains were isolated from the same mangrove forest on the Andaman Sea coastline. They could accumulate lipid when suspended in glucose solution without any supplementation, while the fatty acid composition and oil profile of Rh. sphaerocarpa 11-14.4 and Sait. podzolica 11-11.3.1 were similar to vegetable oil and cocoa butter, respectively.


Assuntos
Filogenia , Áreas Alagadas , Leveduras/classificação , Leveduras/isolamento & purificação , Ascomicetos/química , Ascomicetos/classificação , Ascomicetos/isolamento & purificação , Basidiomycota/química , Basidiomycota/classificação , Basidiomycota/isolamento & purificação , Biodiversidade , Biocombustíveis , DNA Fúngico/análise , DNA Fúngico/isolamento & purificação , Gorduras na Dieta , Ácidos Graxos/análise , Glucose/metabolismo , Metabolismo dos Lipídeos , Lipídeos/análise , Tipagem Molecular , Óleos Vegetais , RNA Ribossômico/genética , Análise de Sequência , Tailândia , Leveduras/química , Leveduras/genética
20.
Fitoterapia ; 137: 104260, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31284016

RESUMO

One new benzophenone derivative, named tenllone I (1), two new eremophilane derivatives lithocarins B (2) and C (3), and a new monoterpentoid lithocarin D (4), together with two know compounds (5 and 6) were isolated from the endophytic fungus Diaporthe lithocarpus A740. All of the structures for these new compounds were fully characterized and established on the basis of extensive spectroscopic interpretation. In addition, all the isolated compounds were evaluated in vitro for their cytotoxic activity. Compounds 2, 3, and 5 showed weak inhibitory activities against tumor cell lines.


Assuntos
Ascomicetos/química , Benzofenonas/isolamento & purificação , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Benzofenonas/farmacologia , Linhagem Celular Tumoral , China , Endófitos/química , Humanos , Estrutura Molecular , Morinda/microbiologia
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