RESUMO
Ten new C9 polyketides (asperochratides A-J, 1-10) and 14 known miscellaneous compounds (11-24) were isolated from the deep-sea-derived fungus Aspergillus ochraceus. Structures of the new compounds were elucidated by extensive spectroscopic analyses, modified Mosher's method, Mo2(OAc)4 induced circular dichroism (ICD) experiments, and ECD calculations. Structurally, compounds 1-11 and 16-18 share the same polyketide origin of the skeleton and belong to aspyrone co-metabolites. All isolates were tested for cytotoxic, anti-food allergic, anti-H1N1 virus, anti-microbe, and anti-inflammatory activities in vitro. Results showed that compounds 5-8 and 13-17 exerted significant cytotoxic effects on BV-2 cell line, and compound 16 showed the potential of anti-inflammatory activities.
Assuntos
Anti-Inflamatórios/química , Antineoplásicos/química , Aspergillus ochraceus/química , Misturas Complexas/química , Policetídeos/química , Água do Mar/microbiologia , Anti-Inflamatórios/farmacologia , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Misturas Complexas/farmacologia , Avaliação Pré-Clínica de Medicamentos , Humanos , Modelos Moleculares , Conformação Molecular , Óxido Nítrico/metabolismo , Policetídeos/farmacologiaRESUMO
The most wide-spread "hostile" environmental factor for marine microorganisms is low temperature, which is usually accompanied by high hydrostatic pressure (HHP). Metabolic mechanisms of marine microorganisms adapting to prolonged low temperature under HHP remain to be clarified. To reveal the underlying metabolic mechanisms, we performed NMR-based metabolomic analysis of aqueous extracts derived from a psychrotolerant Microbacterium sediminis YLB-01, which was isolated from deep-sea sediment and possess great biotechnology potentials. The YLB-01 cells were firstly cultivated at the optimal condition (28 °C, 0.1 MPa) for either 18 h (logarithmic phase) or 24 h (stationary phase), then continually cultivated at either 28 °C or 4 °C under HHP (30 MPa) for 7 days. The cells cultivated at low temperature, which experienced cold stress, were distinctly distinguished from those at normal temperature. Cold stress primarily induced metabolic changes in amino acid metabolism and carbohydrate metabolism. Furthermore, the logarithmic and stationary phase cells cultivated at low temperature exhibited distinct metabolic discrimination, which was mostly reflected in the significantly disturbed carbohydrate metabolism. The logarithmic phase cells displayed suppressed TCA cycle, while the stationary phase cells showed decreased pyruvate and increased lactate. In addition, we performed transcriptome analysis for the stationary phase cells to support the metabolomic analysis. Our results suggest that the cold adaptation of the psychrotroph YLB-01 is closely associated with profoundly altered amino acid metabolism and carbohydrate metabolism. Our work provides a mechanistic understanding of the metabolic adaptation of marine psychrotrophs to prolonged low temperature under HHP.
Assuntos
Actinobacteria/metabolismo , Adaptação Fisiológica , Temperatura Baixa , Pressão Hidrostática , Metabolômica , Actinobacteria/genética , Actinobacteria/crescimento & desenvolvimento , Aminoácidos/metabolismo , Organismos Aquáticos/genética , Organismos Aquáticos/metabolismo , Metabolismo dos Carboidratos , Ciclo do Ácido Cítrico , Resposta ao Choque Frio , Perfilação da Expressão Gênica , Sedimentos Geológicos/microbiologiaRESUMO
Starfishes produce various structurally unique secondary metabolites with diverse biological activities. This review is an update summary of the new compounds and their bioactivities from starfish (the Asteroidea Class) with 71 references covering from January 2007 to December 2018. During this period, 216 new compounds were obtained from 36 species. The chemical constituents are mostly steroids, steroidal glycosides, and gangliosides. These components have been found to possess various bioactivities, including anticancer, anti-inflammation, etc.
Assuntos
Anti-Inflamatórios/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Inflamação/tratamento farmacológico , Neoplasias/tratamento farmacológico , Estrelas-do-Mar/química , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , HumanosRESUMO
A novel ergostane, sarocladione (1), was isolated from the deep-sea-derived fungus Sarocladium kiliense, along with 20 known compounds. The structure of 1 was determined mainly by a detailed analysis of its experimental and calculated NMR spectroscopic data. It is worth noting that 1 was the first steroid bearing a 5,10:8,9-diseco moiety. All 21 compounds were tested for in vitro antitumor activities against five cancer cell lines. ß-Sitostenone (7) and 4,6-dihydroxyeudesmane (20) showed significant effects on HeLa-S3 cells with the IC50 values of 9.2 µM and 9.3 µM, respectively.
Assuntos
Acremonium/química , Antineoplásicos/farmacologia , Secoesteroides/farmacologia , Esteroides/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Conformação Molecular , Secoesteroides/química , Secoesteroides/isolamento & purificação , Esteroides/química , Esteroides/isolamento & purificação , Relação Estrutura-AtividadeRESUMO
Aphidicolin, a potent DNA polymerase α inhibitor, has been explored in clinical trials for the treatment of cancer. So far, about 300 modified aphidicolins have been discovered. However, none have shown a stronger effect. Herein, we report 71 new (aphidicolins A1-A71, 1-71) and eight known (72-79) aphidicolin congeners from Botryotinia fuckeliana MCCC 3A00494, a fungus isolated from the western Pacific Ocean (-5572 m). The structures of 1-71 were determined through extensive spectroscopic analysis, X-ray crystallography, chemical derivatization, modified Mosher's method, and the ECD exciton chirality method. Compounds 54-57 and 58-64 are novel 6/6/5/6/5 pentacyclic aphidicolins featuring tetrahydrofuran and dihydrofuran rings, respectively, while compounds 65-71 are rare noraphidicolins. Aphidicolin A8 (8) significantly induced apoptosis in T24 (IC50 = 2.5 µM) and HL-60 (IC50 = 6.1 µM) cancer cells by causing DNA damage. By docking its structure to the human DNA polymerase α binding pocket, 8 was found to form tight intermolecular contacts, elaborating aphidicolin A8 as a potently cytotoxic lead compound.
Assuntos
Afidicolina/química , Botrytis/química , Biologia Marinha , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Cristalografia por Raios X , Estrutura Molecular , Espectroscopia de Prótons por Ressonância Magnética , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
Five new (fusarisolins Aâ»E, 1 to 5) and three known (6 to 8) polyketides were isolated from the marine-derived fungus Fusarium solani H918, along with six known phenolics (9 to 14). Their structures were established by comprehensive spectroscopic data analyses, methoxyphenylacetic acid (MPA) method, chemical conversion, and by comparison with data reported in the literature. Compounds 1 and 2 are the first two naturally occurring 21 carbons polyketides featuring a rare ß- and γ-lactone unit, respectively. All isolates (1 to 14) were evaluated for their inhibitory effects against tea pathogenic fungus Pestalotiopsis theae and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase gene expression. Compound 8 showed potent antifungal activity with an ED50 value of 55 µM, while 1, 8, 13, and 14 significantly inhibited HMG-CoA synthase gene expression.
Assuntos
Fusarium/química , Policetídeos/química , Policetídeos/farmacologia , Antifúngicos/farmacologia , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Produtos Biológicos/farmacologia , Fusarium/metabolismo , Hidroximetilglutaril-CoA Sintase/metabolismo , Conformação Molecular , Policetídeos/isolamento & purificação , Policetídeos/metabolismoRESUMO
Four new (penigrisacids A-D, 1-4) and one known (5) carotane sesquiterpenoids were isolated from the deep-sea-derived fungus Penicillium griseofulvum, along with four known compounds (6-9). The planar structures and relative configurations of the new compounds were determined by extensive analysis of the NMR and HRESIMS data. The absolute configurations were established by comparison of the experimental and calculated ECD (electronic circular dichroism) spectra or OR (optical rotation) value. Compound 9 exhibited potent anti-food allergic activity with IC50 value of 28.7 µM, while 4 showed weak cytotoxicity against ECA-109 tumor cells (IC50 = 28.7 µM).
Assuntos
Organismos Aquáticos/química , Penicillium/química , Sesquiterpenos/química , Linhagem Celular Tumoral , Dicroísmo Circular , Células HeLa , Humanos , Espectroscopia de Ressonância Magnética/métodos , Oceanos e Mares , Sesquiterpenos/farmacologiaRESUMO
Five new ergostanes, penicisteroids D-H (1-5), were isolated from the liquid culture of the deep-sea-derived fungus Penicillium granulatum MCCC 3A00475, along with 27 known compounds. The structures of the new steroids were established mainly on the basis of extensive analysis of 1D and 2D NMR as well as HRESIMS data. Moreover, the absolute configurations of 1 were confirmed unambiguously by the single-crystal X-ray crystallography. Compounds 2 and 4â»7 showed moderate antiproliferative effects selectively against 12 different cancer cell lines with IC50 values of around 5 µM. Compounds 2 and 6, potent RXRα binders with Kd values of 13.8 and 12.9 µM, respectively, could induce apoptosis by a Retinoid X Receptor (RXR)-α-dependent mechanism by regulating RXRα transcriptional expression and promoting the poly-ADP-ribose polymerase (PARP) cleavage. Moreover, they could inhibit proliferation by cell cycle arrest at the G0/G1 phase.
Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Organismos Aquáticos/química , Ergosterol/farmacologia , Penicillium/química , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cristalografia por Raios X , Ensaios de Seleção de Medicamentos Antitumorais , Ergosterol/análogos & derivados , Ergosterol/química , Ergosterol/isolamento & purificação , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Sedimentos Geológicos/microbiologia , Humanos , Concentração Inibidora 50 , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Receptor X Retinoide alfa/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
A new pimarane diterpenoid, named botryopimarene A (1), was discovered from the fungus Botryotinia fuckeliana MCCC 3â 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 >20â µm).
Assuntos
Abietanos/química , Ascomicetos/química , Diterpenos/química , Água do Mar/microbiologia , Abietanos/isolamento & purificação , Abietanos/farmacologia , Ascomicetos/isolamento & purificação , Ascomicetos/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Dicroísmo Circular , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Humanos , Conformação MolecularRESUMO
Chromatographic separation of the AcOEt extract of the fermented cultures of the deep-sea-derived fungus Graphostroma sp. resulted in the isolation of 11 new chained polyketides, namely graphostromols A-K (1-11). The structures of the new compounds were established by the extensive analyses of their NMR and HR-ESI-MS data. The absolute configuration at C-11 in 1 was determined on the basis of the modified Mosher's method. Compounds 1-5, bearing a 2,2,10,10-tetramethyldodecane skeleton, were discovered for the first time from nature. All isolates were evaluated for their cytotoxicities against five different cancer cell lines (HeLa, Eca-109, Biu-87, Bel-7402, and PANC-1). However, none showed positive effects.
Assuntos
Policetídeos/química , Linhagem Celular Tumoral , Humanos , Espectroscopia de Ressonância Magnética , Conformação Molecular , Policetídeos/isolamento & purificaçãoRESUMO
Marine microorganisms are an important source of natural products with potent bioactivities. Unlike the land, the ocean, especially the deep-sea, is characterized by high pressure, high salinity, low nutrition, and no light among others. Therefore, the biodiversity of marine microorganisms is supposed to be very different from that of the terrestrial ones. Yet, many marine microorganisms can find their counterparts in terrestrial environments. To evaluate their differences, a comparative metabolomics investigation was performed on four strains of Nesterenkonia flava isolated from terrestrial and marine environments. As a result, marine strains were clearly distinguished from terrestrial ones on the principal components analysis (PCA) score plot. Furthermore, by partial least squares discrimination analysis (PLS-DA) and univariate analysis, the characteristic metabolites were figured out and found to be involved in osmotic regulation, redox balancing, and energy metabolism. Our results demonstrated that marine actinomycetes could produce novel secondary metabolites different from their terrestrial relatives because they have special metabolic patterns closely related to the unique features of their living environment.
Assuntos
Actinobacteria/metabolismo , Micrococcaceae/metabolismo , Biodiversidade , Produtos Biológicos/metabolismo , Metabolômica/métodos , Análise de Componente PrincipalRESUMO
A novel cyclic ether, nesterenkoniane (1), was isolated from the deep-sea-derived actinomycete Nesterenkonia flava MCCC 1K00610, together with 12 known compounds, including two macrolides (2, 3), two diketopiperazines (4, 5), two nucleosides (6, 7), two indoles (8, 9), three phenolics (10-12), and one butanol derivate (13). Their structures were established mainly on detailed analysis of the NMR and MS spectroscopic data. All 13 compounds were tested for anti-allergic activities using immunoglobulin E (IgE) mediated rat mast RBL-2H3 cell model. Under the concentration of 20 µg/mL, 1 exhibited moderate anti-allergic activity with inhibition rate of 9.86%, compared to that of 37.41% of the positive control, loratadine. While cyclo(d)-Pro-(d)-Leu (4) and indol-3-carbaldehyde (8) showed the most potent effects with the IC50 values of 69.95 and 57.12 µg/mL, respectively, which was comparable to that of loratadine (IC50 = 35.01 µg/mL). To the best of our knowledge, it is the first report on secondary metabolites from the genus of Nesterenkonia.
Assuntos
Actinobacteria/química , Actinobacteria/metabolismo , Antialérgicos/química , Antialérgicos/farmacologia , Micrococcaceae/química , Micrococcaceae/metabolismo , Animais , Butanóis/química , Butanóis/farmacologia , Linhagem Celular , Dicetopiperazinas/química , Dicetopiperazinas/farmacologia , Imunoglobulina E/metabolismo , Indóis/química , Indóis/farmacologia , Loratadina/farmacologia , Macrolídeos/química , Macrolídeos/farmacologia , Mastócitos/efeitos dos fármacos , Nucleosídeos/química , Nucleosídeos/farmacologia , RatosRESUMO
From the deep-sea-derived fungus Aspergillus candidus, one novel (1) and three known (2-4) p-terphenyl derivates were isolated. The structure of the new compound was established mainly on the basis of extensive analysis of 1D and 2D NMR data. All four isolates were tested for in vitro anti-food allergic and antitumor bioactivities. Compounds 3 and 4 showed potent antiproliferative effect against four cancer cells of Hela, Eca-109, Bel-7402, and PANC-1 with IC50 values ranging from 5.5 µM to 9.4 µM.
Assuntos
Aspergillus/química , Oceanos e Mares , Compostos de Terfenil/farmacologia , Antineoplásicos/farmacologia , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Espectroscopia de Prótons por Ressonância Magnética , Compostos de Terfenil/química , Compostos de Terfenil/isolamento & purificaçãoRESUMO
A high cell density strategy has been used in bioethanol production to shorten the fermentation period. To reveal the molecular basis of fermentative behavior in high cell density, the profiling of the phospholipids and sterols of Saccharomyces cerevisiae during fermentation at five different pitching rates (1, 5, 10, 20, and 40 g/L) was investigated. Using LC/ESI/MS(n) technology, 148 phospholipid species were detected, of which 91 species were quantified, and using the gas chromatography-time-of-flight mass spectrometry procedure, a total of 11 sterols were quantified. Phospholipid samples from different pitching rates were discriminated into three groups using principal component analysis (1, 5 g/L, and the others). The main changes in the lipid profile of yeast cells with higher pitching rates were as follows: (a) the relative contents of phosphatidylglycerol and phosphatidylserine were higher while phosphatidylinositol was lower compared with lower pitching rates, (b) the saturated and the relatively shorter fatty acyl chains of phospholipids decreased, and (c) the content of ergosterol was higher. These findings suggested a regulation of the property of the membrane at the situation of high cell density and a possible approach of self-protection of the yeast cells against the high density stresses.
Assuntos
Fermentação , Fosfolipídeos/metabolismo , Saccharomyces cerevisiae/química , Saccharomyces cerevisiae/metabolismo , Esteróis/metabolismo , Fosfolipídeos/química , Esteróis/químicaRESUMO
Eight unprecedent diterpenoids, botryotins A-H (1-8), were obtained from Botryotinia fuckeliana. They represent three novel carbon skeletons with 6/6/5/5 (1), 6/6/5/6 (2-6), and 6/6/6/5 (7 and 8) tetracyclic scaffolds. Their structures were determined by detailed spectroscopic analysis and chemical derivatization as well as quantum chemical calculation of the ECD and OR data. Botryotin A (1) exhibited a moderate antiallergic effect (IC50 = 0.2 mM). A plausible biosynthetic pathway for 1-8 was proposed.
Assuntos
Antialérgicos/farmacologia , Botrytis/química , Diterpenos/farmacologia , Hipersensibilidade/tratamento farmacológico , Animais , Antialérgicos/química , Antialérgicos/isolamento & purificação , Linhagem Celular Tumoral , Diterpenos/química , Diterpenos/isolamento & purificação , Relação Dose-Resposta a Droga , Humanos , Camundongos , Células RAW 264.7 , RatosRESUMO
An intriguing cage-like polyhemiketal, nesteretal A (1), was isolated from the coral-derived actinomycete Nesterenkonia halobia. Its structure was established by extensive spectroscopic and computational methods. Nesteretal A is a highly oxygenated compound featuring an unprecedented 5/5/5/5 tetracyclic scaffold. A possible biosynthetic pathway of 1 from naturally occurring diacetyl was proposed. Compound 1 showed a weak retinoid X receptor-α (RXRα) transcriptional activation effect.
Assuntos
Actinobacteria/química , Policetídeos/farmacologia , Receptor X Retinoide alfa/antagonistas & inibidores , Linhagem Celular Tumoral , Teoria da Densidade Funcional , Relação Dose-Resposta a Droga , Humanos , Conformação Molecular , Policetídeos/química , Policetídeos/isolamento & purificação , Receptor X Retinoide alfa/metabolismo , Relação Estrutura-AtividadeRESUMO
Two new (1, 2) and one known (3) meroterpenoids were isolated from the deep-sea-derived fungus Penicillium allii-sativi. The relative structures of new compounds were determined on the basis of an extensive analysis of the NMR and MS data, and the absolute configurations were established by ECD calculations. Andrastone A (1) is a rare andrastin bearing an unusual cyclopentan-1,3-dione. It shows a selectively antiproliferative effect against HepG2 tumor cells with an IC50 value of 7.8 µM. Mechanism study showed that apoptosis via Caspase and RXRα pathways are responsible for the inhibitory effect.
RESUMO
BACKGROUND: Knowledge of the compatibility between spirodiclofen and the predator Oligota flavicornis is an important aspect for the management of spider mites. RESULTS: We used the age-stage, two-sex life table to assess the effects of spirodiclofen on the life history traits and population growth of O. flavicornis. At the maximum recommended concentration (60 mg a.i. L-1 ) and also at twice the maximum recommended dosage (120 mg a.i. L-1 ), the preadult stages of O. flavicornis were significantly lengthened, while the adult longevity and fecundity decreased significantly. The finite rate (λ), intrinsic rate of increase (r), and net reproduction rate (R0 ) decreased, while the mean generation time (T) was longer after both the 60 and 120 mg a.i. L-1 treatments than it was in the control and 30 mg a.i. L-1 treatments. Life expectancy and reproductive value were higher in the control and 30 mg a.i. L-1 treatment than in the 60 and 120 mg a.i. L-1 treatments; the two higher concentrations were detrimental to the development of O. flavicornis. CONCLUSION: A proper combination of the O. flavicornis and spirodiclofen to control the spider mite, while avoiding the side effect of spirodiclofen, could be achieved based on the knowledge of life tables. © 2018 Society of Chemical Industry.
Assuntos
4-Butirolactona/análogos & derivados , Acaricidas/efeitos adversos , Besouros/efeitos dos fármacos , Compostos de Espiro/efeitos adversos , 4-Butirolactona/efeitos adversos , Animais , Besouros/crescimento & desenvolvimento , Feminino , Fertilidade , Características de História de Vida , Masculino , Controle Biológico de Vetores , Crescimento Demográfico , Comportamento Predatório , TetranychidaeRESUMO
A genome mining analysis on the deep-sea derived actinomycete Saccharopolyspora cebuensis MCCC 1A09850 indicated its potential to produce polypeptides. Accordingly, a systematic chemical investigation was conducted, which resulted in the isolation of one new cyclic tetrapeptide (saccharopolytide A, 1) and two known polyketides (2, 3) along with six other miscellaneous compounds (4â9). Mainly by analysis of the 1D, 2D NMR and MS data, the chemical structure of saccharopolytide A was established as cyclo-(l-Leu-4-hydroxy-l-Pro-l-Phe-4-hydroxy-l-Pro). All isolates were evaluated for anti-allergic and anti-tumor bioactivities. Indol-3-carbaldehyde (4) showed weak anti-allergic effect with IC50 value of 55.75 µg/mL. And 2 showed weak anti-proliferative activity against Hela and H1299 tumor cell lines. Our results consolidate the potential of deep-sea-derived microorganisms to produce structurally interesting compounds.
Assuntos
Antialérgicos/farmacologia , Antineoplásicos/farmacologia , Peptídeos Cíclicos/química , Saccharopolyspora/química , Antialérgicos/química , Antineoplásicos/química , Organismos Aquáticos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Células HeLa , Humanos , Concentração Inibidora 50 , Espectroscopia de Ressonância Magnética/métodos , Estrutura Molecular , Peptídeos Cíclicos/farmacologia , Prolina/química , Saccharopolyspora/metabolismo , Metabolismo SecundárioRESUMO
Nine new guaianes (graphostromanes A-I, 1-9) were isolated from the deep-sea-derived fungus Graphostroma sp. MCCC 3A00421, along with four known ones (10-13). The relative configurations were established mainly by detailed analysis of the NMR and HRESIMS data, while the absolute configurations were assigned using the X-ray crystallography and modified Mosher's method. All isolates were evaluated for their inhibitory effects against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW264.7 macrophages. Graphostromanes F (6) showed remarkable inhibitory effect with an IC50 value of 14.2 µM, which was even stronger than that of aminoguanidine, a positive control with an IC50 value of 23.4 µM.