RESUMO
Two new naphthyridine compounds, 4-methoxycarbonyl-5-oxo-1,6-naphthyridine (1) and 5-methoxycarbonyl-4-oxo-1,6-naphthyridine (2) were obtained from the MeOH extracts of sponge Aaptos suberitoides. Their structures were determined by spectroscopic methods, including HR-ESI-MS, 1D-NMR (1 H-NMR, 13 C-NMR), 2D-NMR (COSY, HSQC, HMBC). The structure of compound 1 was further confirmed via single crystal X-ray diffraction analysis. Compound 1 was found to reduce NO production in LPS-induced RAW 264.7 macrophages with IC50 value of 0.15â mM. In addition, it decreased the mRNA expression levels of pro-inflammatory mediators, such as the tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX2) in LPS-induced macrophages. It also decreased the protein expression of iNOS and COX-2 in LPS-induced macrophages. Mechanistic studies further revealed that compound 1 inhibited the mitogen-activated protein kinase (MAPK), and activated the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) signaling pathways in LPS-induced RAW 264.7 macrophages.
Assuntos
Lipopolissacarídeos , Proteínas Quinases Ativadas por Mitógeno , Animais , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Proteínas Quinases Ativadas por Mitógeno/farmacologia , Lipopolissacarídeos/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Células RAW 264.7 , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/metabolismo , Transdução de Sinais , Macrófagos , Naftiridinas/farmacologia , Naftiridinas/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Heme Oxigenase-1/metabolismo , Óxido Nítrico/metabolismoRESUMO
Marine fungi can metabolize structurally diverse active components, and have become an important source of drug lead molecules. In the present study, the chemical investigation on the EtOAc extract of the fermentation broth of the marine-derived fungus Trametes sp. ZYX-Z-16 led to the isolation of eight meroterpenoids (1-8), including two undescribed ones, together with ten ergostane steroid analogues (9-18). The structures of two new spiromeroterpenoids, asnovolin H (1) and asnovolin I (2), were determined based on 1D, 2D NMR, and HRESIMS spectroscopic data along with ECD spectra calculations. All compounds were tested for antibacterial and α-glucosidase inhibitory activity. Among them, compound 12 showed definite antibacterial activities against Staphylococcus aureus ATCC 6538 (MIC 32 µg/mL) and Bacillus subtilis ATCC 6633 (MIC 16 µg/mL). In addition, compounds 9 and 10 showed superior inhibitory activity, with IC50 values of 104.1 and 111.3 µM, respectively, to the positive control acarbose (304.6 µM).
Assuntos
Staphylococcus aureus , Trametes , Espectroscopia de Ressonância Magnética , Antibacterianos/química , Esteroides/farmacologia , Testes de Sensibilidade Microbiana , Estrutura MolecularRESUMO
To screen, prepare, identify, and evaluate the activities of natural antioxidants for treating chronic diseases caused by oxidative stress. Two algal proteins, namely ZD10 and ZD60, precipitated with 10 and 60% (NH4)2SO4 were extracted from red algae Eucheuma cottonii (E. cottonii) and hydrolyzed using five proteolytic enzymes. The results showed that ZD60 played the most significant role in the enhancement of 2,2-diphenyl-1-picrylhydrazyl radical (DPPHâ ) scavenging activity (25.91 ± 0.24%) among all protein hydrolysates. Subsequently, six antioxidant peptides (EP1-EP6) were isolated from the papain hydrolysate of ZD60 by ultrafiltration and chromatography methods. Their amino acid sequences were identified as Thr-Ala (EP1), Met-Asn (EP2), Tyr-Ser-Lys-Thr (EP3), Tyr-Ala-Val-Thr (EP4), Tyr-Leu-Leu (EP5), and Phe-Tyr-Lys-Ala (EP6) with molecular weights of 190.21, 263.33, 497.55, 452.51, 407.51, and 527.62 Da, respectively. Of which, EP3, EP4, EP5, and EP6 showed strong scavenging activities on DPPHâ , hydroxyl radical (HOâ ), and superoxide anion radical (O- 2â ). Moreover, EP4 and EP5 could significantly protect human umbilical vein endothelial cells (HUVECs) from H2O2-induced oxidative damage by increasing the levels of antioxidant enzyme systems including superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) to reduce the levels of reactive oxygen species (ROS) (60.51 and 51.74% of model group) and malondialdehyde (MDA) (75.36 and 64.45% of model group). In addition, EP4 and EP5 could effectively inhibit H2O2-induced apoptosis by preventing HUVECs from early apoptosis to late apoptosis. These results indicated that the antioxidant peptides derived from E. cottonii, especially EP4 and EP5, could serve as the natural antioxidants applied in pharmaceutical products to treat chronic cardiovascular diseases caused by oxidative damage, such as coronary heart disease, atherosclerosis, etc.
RESUMO
Chemical investigation of coastal saline soil-derived fungus Aspergillus flavipes RD-13 led to the isolation of two new seco-cytochalasins (1) and (2) along with nine known analogs. Their structures were elucidated by comprehensive spectral analysis, and the absolute configurations of these two new ones were determined through Rh2(OCOCF3)4-induced CD experiment and chemical interconversions. Moreover, the absolute configuration of a known compound named cytochalasins Z18 (3) was also determined for the first time. Structurally, compounds 1, 2 and 3 were the open ring derivatives of compounds 5, 8, and 4, respectively. All compounds were evaluated for their cytotoxic activities on A549, H1299 and H520 cells and 4 exhibited the strongest inhibitory activities towards the above cell lines with IC50 values of 0.15, 0.23 and 0.43 µg/mL, respectively. Preliminary structure-activity relationship analysis suggested the importance of macrocyclic ring in cytochalasins to confer cytotoxicity.
Assuntos
Citocalasinas , Solo , Aspergillus , Citocalasinas/química , Fungos , Estrutura MolecularRESUMO
Three new aaptamines (1-3) together with two known derivatives (4-5) were isolated from the South China Sea sponge Aaptos suberitoides. The structures of all compounds were unambiguously elucidated by spectroscopic analyses as well as the comparison with literature data. All the compounds were evaluated for their cytotoxic activities against five human cancer cell lines including H1299, H520, SCG7901, CNE-2 and SW680 cells. As a result, compounds 3-5 showed moderate cytotoxicities against H1299 and H520 cells with IC50 values ranging from 12.9 to 20.6 µg/mL. Besides, compounds 3-5 also showed potent inhibitory activities toward cyclin-dependent kinase-2 (CDK2) with IC50 values of 14.3, 3.0 and 6.0 µg/mL, respectively. In addition, compounds 3-5 significantly induced G1 arrests of H1299 cells at low concentrations. Drug affinity responsive target stability (DARTS) experiments were carried out and further demonstrated that compound 3 could effectively bind with CDK2 protein and protect it from the degradation by pronase.
Assuntos
Antineoplásicos , Naftiridinas , Humanos , Naftiridinas/química , Antineoplásicos/farmacologia , Antineoplásicos/química , China , Linhagem Celular Tumoral , Quinase 2 Dependente de CiclinaRESUMO
The sea buckthorn (Hippophae rhamnoides L.) berries are rich in various bioactive components and widely used as fruit and traditional medicine. In this study, a novel heteropolysaccharide fraction (SP0.1-1) was isolated from Sea buckthorn berries. SP0.1-1 is composed of mannose, glucose, galactose, and arabinose in the molar ratio of 1:2.3:1.9:11.2 with a core structure containing 1,4-linked-α-d-Glcp, 1,4,6-linked-α-d-Glcp and 1,4-linked-α-d-Manp residues as the backbone. And the side-chains comprised of 1,3,5-linked-α-l-Araf, 1,5-linked-α-l-Araf, terminal α-Araf and 1,4-linked-ß-d-Galp. Furthermore, a diet supplemented with SP0.1-1 extended the mean lifespan, enhanced antioxidant enzyme (superoxide dismutase, SOD; glutathione peroxidase, GSH-Px; and catalase, CAT) activities, and decreased the malondialdehyde (MDA) level and hydrogen peroxide (H2O2)-induced mortality rate in fruit flies (Drosophila melanogaster). To summarize, the study's findings will provide evidence for the development of sea buckthorn polysaccharide products.
Assuntos
Envelhecimento/efeitos dos fármacos , Antioxidantes , Drosophila melanogaster/efeitos dos fármacos , Hippophae/metabolismo , Polissacarídeos , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Polissacarídeos/química , Polissacarídeos/farmacologiaRESUMO
A polysaccharide, CSL-0.1, was isolated from the medicinal lichen, Usnea longissima. CSL-0.1 was a neutral rhamnose-containing glucogalactomannan with a molecular weight of 7.86 × 104 Da. The polysaccharide had a core mannan structure with (1 â 6)-α-d-Manp units as the main chain and was substituted at the O-2 positions with side chains containing (1 â 2)-α-d-Manp residue, [3)-α-Glcp(1 â 4)-α-Glcp(1â] and 6-O-substituted ß-d-Galf units. 2-O- and 2,3-di-O-substituted Rhap units. The effects of CSL-0.1 on intestinal immunity and antioxidant activity were evaluated. CSL-0.1 increased the spleen and thymus indices in a dose-dependent manner and conferred immunomodulation on reversing the Th1/Th2-related cytokine imbalance in cyclophosphamide (CP)-induced immunosuppressed mice. CSL-0.1 could also enhance the levels of secretory immunoglobulin A in CP-injected mice. Additionally, the antioxidant levels in the liver and intestine of the mice were increased 20%-50% after intragastric injection by CSL-0.1.
Assuntos
Imunização , Líquens/química , Parmeliaceae/química , Polissacarídeos/farmacologia , Animais , Antioxidantes/farmacologia , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Citocinas/metabolismo , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Hidrólise , Intestinos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Metilação , Camundongos Endogâmicos ICR , Monossacarídeos/análise , Polissacarídeos/isolamento & purificação , Espectroscopia de Prótons por Ressonância Magnética , Espectrofotometria Infravermelho , Baço/efeitos dos fármacos , Timo/efeitos dos fármacosRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Shiraia bambusicola is a parasitic fungus on the twigs of bamboos. Its relatively large stroma has high medicinal value and can treat a variety of diseases such as rheumatoid arthritis, cold stomach pain, sciatica, injuries, chronic bronchitis, and infantile. It is widely distributed in many provinces in Southern China and also is also found in Japan. AIM OF THE STUDY: Medicinal fungi were important resources for bioactive polysaccharides. To explore bioactive polysaccharides from Shiraia bambusicola, a heteropolysaccharide SB2-1 was purified and obtained from S. bambusicola and its immunostimulating activity was researched. MATERIALS AND METHODS: The polysaccharide from S. bambusicola was extracted and purified using enzyme assisted extraction, ethanol precipitation, anion-exchange and size-exclusion chromatography. Molecular weight of polysaccharide was estimated by high performance gel permeation chromatography. Monosaccharide compositions were determined by high performance liquid chromatography after pre-column derivatization and UV detection. Structure information was elucidated by IR spectrum, GC-MS analysis after methylation and gradual acid hydrolysis of the polysaccharide. The RAW264.7 cells were used to study the immunostimulating activity in vitro. RESULTS: Physicochemical and structural analyses showed that SB2-1 was a neutral heteropolysaccharide with molecular weight at 22.2 kDa and consisted of glucose, galactose and mannose at a ratio of 2.0:1.5:1.0. The structure of SB2-1 was a branched polysaccharides composed of a mannan core and side chains consisted of glucose and galactose. The mannan core was composed of (1â2)-Manp as the main chain. Glucose with (1â4)-D-Glcp, (1â2)-D-Glcp and (1â6)-D-Glcp at different degrees of polymerization were linked at C-6 and C-3 of the (1â2)-Manp as the side chains. The galactose with the linages of (1â6)-D-Galf, â2)-D-Galf(1â and terminal D-Galf(1â also existed in the side chain. The study on the immunostimulating activities of SB2-1 and its core structure P-2 were investigated on RAW264.7 macrophages. The results showed that SB2-1 could activate RAW264.7 macrophage and significantly improve its phagocytic ability by neutral red uptake experiment. Meanwhile, SB2-1 increased significantly higher inducible nitric oxide synthase (iNOS) production and the productions of IL-1, IL-6, IL-12 and TNF-α. The effect of SB2-1 was better than its core structure P-2 produced by gradual acid hydrolysis, which meant the side chains played an important role in the immunostimulating activities. CONCLUSIONS: The investigation demonstrated that the galactofuranose-containing mannogalactoglucan was characteristic polysaccharides in S. bambusicola and could enhance the activation of macrophages.
Assuntos
Adjuvantes Imunológicos/química , Adjuvantes Imunológicos/farmacologia , Ascomicetos/química , Polissacarídeos Fúngicos/química , Polissacarídeos Fúngicos/farmacologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Camundongos , Células RAW 264.7RESUMO
Camellia oleifera is an important Chinese commercial crop. Camellia oleifera can display abnormal leaves due to infection by the parasitic fungus Exobasidium gracile. Exobasidium gracile was isolated from infected leaves and used in fermentation, and exopolysaccharides EP0-1 and EP0.5-1 were purified from the fermentation broth. EP0-1 was an alkaline polysaccharide consisting mainly of the linkages α-d-Manp(1â, â2)-α-d-Manp(1â and â6)-α-d-Manp(1â, â3)-α-d-Glcp(1â andâ4)-α-d-Glcp(1â, terminal ß-d-Galf, (1â5)-ß-d-Galf, and terminal ß-D-GlcN(1â. EP0.5-1 was an acidic galactofuranose-containing polysaccharide. It contained the linkages of α-d-Manp(1â, â2)-α-d-Manp(1â, â6)-α-d-Manp(1â,â2, 6)-α-d-Manp(1â, â4)-α-d-Glcp(1â, and â4)-α-d-GlcUA(1â. Galactofuranose linkages were composed of terminal ß-d-Galf, (1â6)-ß-d-Galf and (1â2)-ß-d-Galf. Exobasidium gracile exopolysaccharides displayed significant immunoregulatory activity by activating macrophages. This research indicates that infected leaves from Camellia oleifera including the exopolysaccharides produced by the parasitic fungus Exobasidium gracile by are worth further investigation as a functional product.
Assuntos
Basidiomycota , Camellia/química , Camellia/microbiologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Polissacarídeos/química , Polissacarídeos/farmacologia , Basidiomycota/química , Basidiomycota/fisiologia , Fenômenos Químicos , Fermentação , Polissacarídeos Fúngicos/química , Polissacarídeos Fúngicos/isolamento & purificação , Polissacarídeos Fúngicos/farmacologia , Macrófagos/imunologia , Macrófagos/metabolismo , Espectroscopia de Ressonância Magnética , Metilação , Doenças das Plantas/microbiologia , Espécies Reativas de Oxigênio/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier , Ácidos Urônicos/metabolismoRESUMO
To study the nutritional composition of Indian Moringa oleifera seed and the antioxidant activity of M. oleifera seed polypeptide, Indian M. oleifera seed was used as raw material for composition analysis and content determination. After extraction of the seed protein, enzymatic hydrolysis with flavourzyme, dispase, papain, pepsin, and alcalase was conducted for different time, and the optimal enzymatic hydrolysis conditions was determined with DPPH scavenging capacity as an indicator. The seed polypeptides obtained by enzymatic hydrolysis were ultrafiltered, and the active peptide fragments were tracked with DPPH, HO (â¢OH), ABTS and superoxide anion (O2â¢-) free radical scavenging ability and lipid oxidation inhibition rate as indicators. The results showed that the protein content in Indian M. oleifera seed was high to 40.34%, containing seven essential amino acids. The content of macroelements such as potassium, sodium, and magnesium is high, with the potassium content as high as 2,357.71 mg/kg, among the microelements, the iron content as high as 36.2 mg/kg. The optimum enzymatic hydrolysis conditions were as follows: enzymatic hydrolysis with flavourzyme (50°C, pH 6.7) for 300 min, and DPPH scavenging capacity was 84.76%. Activity tracing found that the polypeptide fragment with molecular weight <3.5 kDa had the strongest antioxidant capacity, and the EC50 values of DPPH, â¢OH, ABTS, and O2â¢- free radical scavenging rates were 4.0, 4.2, 5.3, and 4.3 mg/ml, respectively. The above results show that Indian M. oleifera seed not only has high nutritional value, but its protease enzymatic hydrolyzate also has significant antioxidant activity, which can be further developed into nutrition products, healthcare products, functional foods, beauty and skin care products, liver protection drugs, etc.
RESUMO
To explore bioactive polysaccharides from the byproducts of squid processing, a heteropolysaccharide, named SV2-1, was isolated from the viscera of squid Ommastrephes bartrami by autolysis, anion-exchange and gel-permeation chromatography and measured for its neuroprotective activity. It was a homogeneous polysaccharide with a molecular weight of 2.3 kDa by HPSEC analysis. SV2-1 contained glucuronic acid, galactosamine and fucose in the ratio of 1.0:1.1:1.2. Its structural characteristics were elucidated by methylation analysis, gas chromatography-mass spectrometry (GC-MS), and nuclear magnetic resonance (NMR). The backbone of SV2-1 was composed of alternant â4)-α-l-Fucp-(1â and â3)-ß-d-GlcUA-(1â Most of â4)-α-l-Fucp-(1â (90%) was substituted by single α-d-GlcNAc as the branches. SV2-1 can protect against the death of PC12 induced by 6-OHDA, and effectively improves cell viability and reduces extracellular LDH release in PC12 cells after injury. Moreover, SV2-1 significantly increases SOD activity but decreases MDA levels.
Assuntos
Decapodiformes/química , Polissacarídeos/química , Polissacarídeos/farmacologia , Animais , Configuração de Carboidratos , Cromatografia em Gel , Cromatografia Gasosa-Espectrometria de Massas , Espectroscopia de Ressonância Magnética , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Fármacos Neuroprotetores/farmacologia , Células PC12 , Polissacarídeos/isolamento & purificação , Ratos , Vísceras/químicaRESUMO
To explore bioactive polysaccharides from medicinal fungi, a homogeneous heteropolysaccharide SB1-1 was extracted from the stroma of Shiraia bambusicola by enzyme assisted extraction, ethanol precipitation, anion-exchange and size-exclusion chromatographies. Chemical and spectroscopic analyses showed that SB1-1 was a neutral polysaccharide composed of mannose, glucose and galactose at a molar ratio of 1.1:1.9:1.0, and had a molecular weight of 18.3â¯kDa. SB1-1 was composed of a mannan core and glucose and galactose side chains. The mannan core was composed of (1â¯ââ¯2)-α-Manp substituted by the side chains (1â¯ââ¯6)-α-d-Manp, (1â¯ââ¯4)-α-d-Glcp and (1â¯ââ¯6)-α-d-Glcp with different degrees of polymerization at the C-6. The galactose side chains had the backbone of (1â¯ââ¯6)-ß-d-Galf. There were two branch sites on every five sugars on average at the O-2 of â6)-ß-Galf(1â, and the branches consisted of â2)-ß-d-Galf(1â and terminal ß-d-Galf(1â. The potential immunomodulatory activities of SB1-1 on RAW264.7 macrophages were investigated. The results showed that SB1-1 could activate macrophage and significantly improve its phagocytic ability by neutral red uptake assay. Additionally, SB1-1 enhanced the productions of IL-1, IL-6, IL-12 and TNF-α in the RAW264.7 macrophages by stimulation of SB1-1, while significantly increased the production of inducible nitric oxide synthase (iNOS) production. This study demonstrated that the galactofuranose-containing polysaccharide SB1-1 from S. bambusicola which is a novel mannogalactoglucan, could enhance the activation of macrophages.
Assuntos
Ascomicetos/química , Polissacarídeos Fúngicos/química , Polissacarídeos Fúngicos/farmacologia , Galactose/química , Fatores Imunológicos/química , Fatores Imunológicos/farmacologia , Animais , Sequência de Carboidratos , Concentração de Íons de Hidrogênio , Hidrólise , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Metilação , Camundongos , Monossacarídeos/análise , Células RAW 264.7RESUMO
Malaria, caused by protozoan parasites of the genus Plasmodium especially by the most prevalent parasite Plasmodium falciparum, represents one of the most devastating and common infectious disease globally. Nearly half of the world population is under the risk of being infected, and more than 200 million new clinical cases with around half a million deaths occur annually. Drug therapy is the mainstay of antimalarial therapy, yet current drugs are threatened by the development of resistance, so it's imperative to develop new antimalarials with great potency against both drug-susceptible and drug-resistant malaria. Triazoles, bearing a five-membered heterocyclic ring with three nitrogen atoms, exhibit promising in vitro antiplasmodial and in vivo antimalarial activities. Moreover, several triazole-based drugs have already used in clinics for the treatment of various diseases, demonstrating the excellent pharmaceutical profiles. Therefore, triazole derivatives have the potential for clinical deployment in the control and eradication of malaria. This review covers the recent advances of triazole derivatives especially triazole hybrids as potential antimalarials. The structure-activity relationship is also discussed to provide an insight for rational designs of more efficient antimalarial candidates.
Assuntos
Antimaláricos/química , Antimaláricos/farmacologia , Plasmodium/efeitos dos fármacos , Triazóis/química , Triazóis/farmacologia , Animais , Humanos , Testes de Sensibilidade ParasitáriaRESUMO
Quinoline and quinolone motifs which act as structural subunits of more complex natural products are ubiquitous in nature, and they are useful pharmacophores which play a pivotal role in drug development. Compared with the corresponding monomeric compounds, the dimers usually exhibited some unique properties, so dimers have caused great interests in recent years. Quinline and quinolone dimers possess various biological properties such as antibacterial, anticancer, antimalarial and antitubercular activities, and some of them which are exemplified by piperaquine have already used in clinical practice. Numerous quinline and quinolone dimers have been synthesized and screened for their in vitro and in vivo biological activities, and some of them exhibited promising potency. Therefore, quinline and quinolone dimers have the potential for clinical deployment in the control and eradication of various diseases. This review covers the recent advances of quinline and quinolone dimers as bioactive substances. The structure-activity relationship was also discussed to provide an insight for rational designs of more active quinline and quinolone dimers.
Assuntos
Antibacterianos/farmacologia , Antimaláricos/farmacologia , Antineoplásicos/farmacologia , Neoplasias/tratamento farmacológico , Quinolinas/farmacologia , Quinolonas/farmacologia , Antibacterianos/química , Antimaláricos/química , Antineoplásicos/química , Bactérias/efeitos dos fármacos , Dimerização , Humanos , Quinolinas/química , Quinolonas/químicaRESUMO
A chemical-epigenetic method was used to enhance the chemodiversity of a marine algicolous fungus. Apart from thirteen known compounds, (+)-brevianamide R ((+)-3), (â)-brevianamide R ((â)-3), (+)-brevianamide Q ((+)-4), (â)-brevianamide Q ((â)-4), brevianamide V ((+)-5), brevianamide W ((â)-5), brevianamide K (6), diorcinol B (7), diorcinol C (8), diorcinol E (9), diorcinol J (10), diorcinol (11), 4-methoxycarbonyldiorcinol (12), two new compounds, (+)- and (â)-brevianamide X ((+)- and (â)- 2)), as well as a new naturally occurring one, 3-[6-(2-methylpropyl)-2-oxo-1H-pyrazin-3-yl]propanamide (1), were isolated from chemical-epigenetic cultures of Aspergillus versicolor OUCMDZ-2738 with 10 µM vorinostat (SAHA). Compared to cultures in the same medium without SAHA, compounds 1â»4, 8, 9, 11, and 12 were solely observed under SAHA condition. The structures of these compounds were elucidated based on spectroscopic analysis, specific rotation analysis, ECD, and X-ray crystallographic analysis. (±)-3, (±)-4, and (±)-5 were further resolved into the corresponding optically pure enantiomers and their absolute configurations were determined for the first time. Compounds 11 and 12 showed selective antibacterial against Pseudomonas aeruginosa with a minimum inhibitory concentration (MIC) of 17.4 and 13.9 µM, respectively. Compound 10 exhibited better α-glucosidase inhibitory activity than the assay control acarbose with IC50 values of 117.3 and 255.3 µM, respectively.
Assuntos
Antibacterianos/farmacologia , Aspergillus/química , Produtos Biológicos/farmacologia , Inibidores de Glicosídeo Hidrolases/farmacologia , Ulva/microbiologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antibacterianos/metabolismo , Aspergillus/efeitos dos fármacos , Aspergillus/genética , Aspergillus/metabolismo , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Produtos Biológicos/metabolismo , Vias Biossintéticas/genética , Engenharia Química/métodos , Cristalografia por Raios X , Dicetopiperazinas/química , Dicetopiperazinas/isolamento & purificação , Dicetopiperazinas/metabolismo , Dicetopiperazinas/farmacologia , Ensaios Enzimáticos , Epigênese Genética/efeitos dos fármacos , Fermentação , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Concentração Inibidora 50 , Metilação/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Éteres Fenílicos/química , Éteres Fenílicos/isolamento & purificação , Éteres Fenílicos/metabolismo , Éteres Fenílicos/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Estereoisomerismo , Vorinostat/farmacologia , alfa-Glucosidases/metabolismoRESUMO
A water-soluble low molecularâ»weight polysaccharide named UP2-1 was isolated and purified from the marine green algae Ulothrixflacca using ion-exchange and size-exclusion chromatography. Composition and characteristics analyses showed that UP2-1 was a sulfated glucuronorhamnan consisting of rhamnose and glucuronic acid in a ratio of 2:1 with 21% sulfate content and a molecular weight of 5.0 kDa. Structural properties were determined using desulfation and methylation analyses combined with infrared spectrum (IR), gas chromatography-mass spectrometer (GC-MS) and nuclear magnetic resonance (NMR). The results showed that UP2-1 was a type of ulvan composed of alternate 4-linked-α-L-rhamnose residues (â4)-α-L-Rha(1â) and 4-linked-ß-D-glucouronoc acid residues. The sulfate groups were mainly present in the O-3 position of â4)-α-L-Rha(1â. Most (70%) of the rhamnose was sulfated. UP2-1 also had a small amount of â4)-α-L-Rha(1â branch at the O-2 position of the â4)-α-L-Rha(1â. UP2-1 exhibited significant anticoagulant and immunomodulating activity in vitro. This study demonstrated that the green algae Ulothrix flacca, which is used as a food and traditional marine herb in China, could also be considered as a source of bioactive ulvan.
Assuntos
Clorófitas/química , Polissacarídeos/química , Anticoagulantes/química , Ácido Glucurônico/química , Espectroscopia de Ressonância Magnética/métodos , Peso Molecular , Ramnose/química , Sulfatos/químicaRESUMO
Two new pimarane diterpenes, libertellenone M (1) and libertellenone N (2), together with five known compounds were isolated from the culture extract of Eutypella sp. D-1 derived from high-latitude soil of the Arctic. The structures of these compounds were determined by spectroscopic data as well as experimental and calculated electronic circular dichroism (ECD) analysis. Antimicrobial and cytotoxic activities of the isolated compounds were evaluated. Compound 3 exhibited weak antibacterial activity against Escherichia coli, Bacillus subtilis, and Vibrio vulnificus, each with MIC values of 16 µg/mL. Compounds 2 and 3 showed moderate cytotoxic activity against K562 and MCF-7 cell lines with IC50 values of 7.67 and 9.57 µm, respectively.
Assuntos
Abietanos/farmacologia , Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Ascomicetos/química , Abietanos/química , Abietanos/isolamento & purificação , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Regiões Árticas , Bacillus subtilis/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Escherichia coli/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Conformação Molecular , Extratos Vegetais/química , Relação Estrutura-Atividade , Vibrio vulnificus/efeitos dos fármacosRESUMO
A coral-associated fungus Penicillium sp.gxwz446 that produced exopolysaccharde was isolated from the coral Echinogorgia flora in South China. Two neutral exopolysaccharides GX1-1 and GX2-1 were obtained from the fermented broth of the fungus and purified by anion-exchange and gel-permeation chromatography. Chemical and spectroscopic analyses showed that GX1-1 was a glucan, primarily composed of glucose, with a molecular weight of 5.0 kDa. GX1-1 mainly consists of (1â4)-linked α-d-glucopyranose units as the backbone, substituted at C-2 with a single α-d-glucopyranose on every sixth sugar residues. GX2-1 was a galactofuranose-containing mannogalactoglucan with a molecular weight of 9.5 kDa. The main linkages were composed of (1â4)-ß-d-Glcp, (1â5)-ß-d-Galf, (1â3,5)-ß-d-Galf, (1â6)-α-d-Manp and (1â2, 6)-α-d-Manp. GX1-1 showed RAW264.7 macrophage activation activity. After subjecting GX1-1 to sulfated modification, there was about one sulfate substitution on every sugar ring, primarily at O-6. The sulfated derivative of GX1-1 exhibited a more significant ability to promote the pinocytic activity of RAW264.7 cells and induce the production of NO.
Assuntos
Antozoários/microbiologia , Polissacarídeos Fúngicos/química , Polissacarídeos Fúngicos/imunologia , Fungos/química , Ativação de Macrófagos/imunologia , Macrófagos/imunologia , Sulfatos/química , Animais , Linhagem Celular , Polissacarídeos Fúngicos/isolamento & purificação , Glucose/química , Macrófagos/metabolismo , Espectroscopia de Ressonância Magnética , Camundongos , Peso Molecular , Óxido Nítrico/biossínteseRESUMO
Two new indole-diterpenoids (1 and 2) and a new isocoumarin (3), along with the known ß-aflatrem (4), paspalinine (5), leporin B (6), α-cyclopiazonic acid (7), iso-α-cyclopiazonic acid (8), ditryptophenaline (9), aflatoxin B1 (10), 7-O-acetylkojic acid (11) and kojic acid (12), were isolated from the fermentation broth of the marine-derived fungus, Aspergillus flavus OUCMDZ-2205. The structures of Compounds 1-12 were elucidated by spectroscopic analyses, quantum ECD calculations and the chemical method. New Compound 1 exhibited antibacterial activity against Staphylococcus aureus with a MIC value of 20.5 µM. Both new Compounds 1 and 2 could arrest the A549 cell cycle in the S phase at a concentration of 10 µM. Compound 1 showed PKC-beta inhibition with an IC50 value of 15.6 µM. In addition, the absolute configurations of the known compounds, 4-6 and leporin A (6a), were also determined for the first time.
Assuntos
Antibacterianos/isolamento & purificação , Aspergillus flavus/metabolismo , Diterpenos/isolamento & purificação , Indóis/isolamento & purificação , Isocumarinas/isolamento & purificação , Penaeidae/microbiologia , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Dicroísmo Circular , Diterpenos/química , Diterpenos/farmacologia , Indóis/química , Indóis/farmacologia , Isocumarinas/química , Isocumarinas/farmacologia , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade MicrobianaRESUMO
To obtain structurally novel and bioactive natural compounds from marine-derived microorganisms, the effect of high salt stress on secondary metabolite production in the marine-derived fungal strain, Spicaria elegans KLA-03, was investigated. The organism, which was isolated from marine sediment, produced different secondary metabolites when cultured in 3% and 10% saline conditions. Four characteristic metabolites, only produced in the 10% salinity culture, were isolated, and their structures were identified as (2E,2'Z)-3,3'-(6,6'-dihydroxybiphenyl-3,3'-diyl)diacrylic acid (1), aspulvinone E (2), aspochalasin E (3) and trichodermamide B (6), according to their 1D and 2D NMR spectra. Compound 1 is a new compound. High salt stress may therefore be a promising means to induce the production of new and chlorinated compounds in halotolerant fungi. Compound 1 showed moderate antibacterial activity against Pseudomonas aeruginosa and Escherichia coli with minimum inhibitory concentration (MIC) values of 0.038 and 0.767 mM, respectively.