RESUMEN
Sea cucumber-derived fungi have attracted much attention due to their capacity to produce an incredible variety of secondary metabolites. Genome-wide information on Aspergillus micronesiensis H39 obtained using third-generation sequencing technology (PacBio-SMRT) showed that the strain contains nonribosomal peptide synthetase (NRPS)-like gene clusters, which aroused our interest in mining its secondary metabolites. 11 known compounds (1-11), including two γ-aromatic butenolides (γ-AB) and five cytochalasans, were isolated from A. micronesiensis H39. The structures of the compounds were determined by NMR and ESIMS, and comparison with those reported in the literature. From the perspective of biogenetic origins, the γ-butyrolactone core of compounds 1 and 2 was assembled by NRPS-like enzyme. All of the obtained compounds showed no inhibitory activity against drug-resistant bacteria and fungi, as well as compounds 1 and 2 had no anti-angiogenic activity against zebrafish.
Asunto(s)
4-Butirolactona , 4-Butirolactona/análogos & derivados , Aspergillus , Familia de Multigenes , Péptido Sintasas , Péptido Sintasas/genética , Estructura Molecular , 4-Butirolactona/farmacología , 4-Butirolactona/química , Aspergillus/enzimología , Aspergillus/química , Aspergillus/genética , Animales , Pez CebraRESUMEN
Three new lupane-triterpenoids (1-3) along with six known compounds (4-9) were isolated from the ethanolic extract of whole plant of Potentilla discolor Bunge. The structures of Compounds 1-3 were established by extensive 1D and 2D NMR together with other spectrum analysis, indicating that their C-27 positions were highly oxygenated, which were rarely found in nature. Their in vitro anti-proliferative activities against HepG-2, MCF-7 and T-84 cell lines were evaluated by Cell Counting Kit-8 (CCK-8) assay, and the results showed different activities for three cell lines with IC50 values ranging from 17.84 to 40.64 µM. In addition, the results from Hoechst 33258 and AO/EB staining as well as annexinV-FITC assays exhibited Compound 1 caused a markedly increased HepG-2 cellular apoptosis in a dose-dependent manner. The further mechanisms of Compound 1-induced cellular apoptosis were confirmed that 1 induced the production of ROS and the alteration of pro- and anti-apoptotic proteins, which led to the dysfunction of mitochondria and activation of caspase-9 and caspase-3 and finally caused cellular apoptosis. These results would be useful in search for new potential antitumor agents and for developing semisynthetic lupane-triterpenoid derivatives with high antitumor activity.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Ácidos Carboxílicos/química , Potentilla/química , Triterpenos/farmacología , Antineoplásicos Fitogénicos/química , Ensayos de Selección de Medicamentos Antitumorales , Células Hep G2 , Humanos , Triterpenos/químicaRESUMEN
OBJECTIVE: To get active secondary metabolites from the fungus Paecilomyces sp.. METHODS: The strain Paecilomyces sp. was further grown in solid-substrate fermentation cultures, the metabolites were got by application of different separation techniques, such as silica gel, Sephadex LH-20 column chromatography, and reversed-phase high performance liquid chromatography. Their structures were identified by comprehensive spectroscopic methods. RESULTS: Four compounds were isolated and identified as Cerebroside C (1), Cerebroside D (2), 2-Hydroxybenzyl alcohol (3), 2-(4-Hydroxyphenyl) ethanol. CONCLUSION: Four compounds are isolated from Paecilomyces sp. for the first time.
Asunto(s)
Alcoholes Bencílicos/aislamiento & purificación , Cerebrósidos/aislamiento & purificación , Paecilomyces/química , Alcohol Feniletílico/análogos & derivados , Alcoholes Bencílicos/química , Cerebrósidos/química , Cromatografía Líquida de Alta Presión , Fermentación , Estructura Molecular , Paecilomyces/metabolismo , Alcohol Feniletílico/química , Alcohol Feniletílico/aislamiento & purificaciónRESUMEN
Bioactivity-directed fractionation of the extract of the mangrove endophytic fungus Talaromyces sp. ZH-154, which was isolated from the stem bark of Kandelia candel (L.) Druce, Rhizophoraceae, afforded two new metabolites, 7-epiaustdiol ( 1) and 8-O-methylepiaustdiol ( 2), together with the known compounds, stemphyperylenol ( 3), skyrin ( 4), secalonic acid A ( 5), emodin ( 6), and norlichexanthone ( 7). Their structures were elucidated on the basis of spectroscopic evidences including CD, MS, and 1D, 2D NMR techniques. The absolute configuration of 1 was unequivocally determined by single-crystal X-ray diffraction. All isolated compounds were evaluated for their antimicrobial and in vitro cytotoxic activities.
Asunto(s)
Antineoplásicos/aislamiento & purificación , Benzopiranos/aislamiento & purificación , Rhizophoraceae/química , Talaromyces/metabolismo , Antracenos/química , Antracenos/aislamiento & purificación , Antracenos/farmacología , Antineoplásicos/química , Antineoplásicos/farmacología , Benzopiranos/química , Benzopiranos/farmacología , Línea Celular Tumoral/efectos de los fármacos , Cristalografía por Rayos X , Humanos , Espectroscopía de Resonancia Magnética , Estructura Molecular , Micorrizas/metabolismo , Corteza de la Planta , Tallos de la Planta , Difracción de Rayos XRESUMEN
OBJECTIVE: The metabolites of HS-3 associated with holothurians were studied, which was identified by molecular biology as Alternaria sp.. METHODS: The holothurians were gathered from the Sea of Zhifu Islet, Shandong Province. HS-3 Alternaria sp. was culternitived in potato medium, and four compound was got by TLC, chromatography and HPLC, and 1-hydroxyl-3-methylanthracene-9,10-dione (1), chrysophanol (2), sterigmatocystin (3) and cerebroside (4) were elucated by modern spectrum. CONCLUSION: All of this provides scientific data for further study of holothurians, and the four coumpouns are isolated from the microbe associated with holothurians for the first time.
Asunto(s)
Alternaria/química , Antraquinonas/aislamiento & purificación , Pepinos de Mar/microbiología , Esterigmatocistina/aislamiento & purificación , Alternaria/metabolismo , Animales , Antraquinonas/química , Cerebrósidos/química , Cerebrósidos/aislamiento & purificación , Fermentación , Espectroscopía de Resonancia Magnética , Estructura Molecular , Esterigmatocistina/químicaRESUMEN
OBJECTIVE: To get active metabolites from the microbes associated with sea cucumber. METHODS: Fungus was isolated from the sea cucumber, and the species was identified by molecular biology, and then was cultivated in GYP medium, and the metabolites were got by chromatography. Their structures were identified by comprehensive spectroscopic methods. RESULTS: Fungus HS-1 Epicocum sp. was isolated from the sea cucumber in Weihai, Yellow Sea. Four compounds were got as 5-methyl-6-hydroxy-8-methyoxy-3-methylisochroman (1), 8-hydroxy-3-methylisochroman-1-one (2), peroxy-ergosterol (3) and succinic acid (4). CONCLUSION: Fungus HS-1 Epicocum spp. is first isolated from the sea cucumber sample, this research provides new idea for further development of sea cucumber.
Asunto(s)
Hongos/química , Feromonas/aislamiento & purificación , Pepinos de Mar/microbiología , Ácido Succínico/aislamiento & purificación , Animales , Ergosterol/química , Ergosterol/aislamiento & purificación , Hongos/aislamiento & purificación , Hongos/metabolismo , Biología Marina , Estructura Molecular , Feromonas/química , Ácido Succínico/químicaRESUMEN
OBJECTIVE: The secondary metabolites of the fungus ZZF13 isolated from the leaves of the mangrove sample Kandelia candel in Zhanjiang and Guignardia sp. 4382 isolated from bark of Kandelia candel (endophyte) of Mai Po, Hong Kong were studied. METHODS: The compounds were isolated by siliga gel, and their structures were identified by IR, MS and NMR. RESULTS: Four compounds were isolated from the culture of this strain. Their structures were identified as Bacillpsporin C (1), 5-carboxymellein (2), 5-methylmellein (3) and 1-(2,6-dihydroxyphenyl) butanone (4). CONCLUSION: The compounds 2 - 4 are isolated from the Guignardia sp. of Marine fungi for the first time.
Asunto(s)
Butanonas/aislamiento & purificación , Hongos/química , Isocumarinas/aislamiento & purificación , Rhizophoraceae/microbiología , Ascomicetos/química , Ascomicetos/crecimiento & desarrollo , Butanonas/química , China , Hongos/metabolismo , Isocumarinas/química , Espectroscopía de Resonancia Magnética , Estructura Molecular , Océanos y Mares , Corteza de la Planta/químicaRESUMEN
The anticancer activities of secalonic acid D separated from the secondary metabolites of the mangrove endophytic fungus No. ZSU44 were investigated in this study. Secalonic acid D showed potent cytotoxicity to HL60 and K562 cells, and the IC(50) values were 0.38 and 0.43 mumol/L, respectively. Annexin V-FITC/PI assay and western blot indicated that secalonic acid D induced apoptosis in HL60 and K562 cells. In addition, secalonic acid D led to cell cycle arrest of G(1) phase related to downregulation of c-Myc. Moreover, our data indicated that downregulation of c-Myc and cell cycle arrest of G(1) phase were caused not by formation of G-quadruplex structures but by activation of GSK-3beta followed by degradation of beta-catenin.
Asunto(s)
Antineoplásicos/farmacología , Apoptosis , Glucógeno Sintasa Quinasa 3/metabolismo , Proteínas Proto-Oncogénicas c-myc/metabolismo , Xantonas/farmacología , beta Catenina/metabolismo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Fase G1/efectos de los fármacos , Fase G1/fisiología , Glucógeno Sintasa Quinasa 3/efectos de los fármacos , Glucógeno Sintasa Quinasa 3 beta , Células HL-60 , Humanos , Proteínas Proto-Oncogénicas c-myc/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-myc/genética , ARN Interferente Pequeño/metabolismo , Xantonas/toxicidad , beta Catenina/antagonistas & inhibidoresRESUMEN
AIM: To investigate the antioxidant activity of chito-oligosaccharides (COSs) on pancreatic islet cells in diabetic rats induced by streptozotocin. METHODS: The antioxidant effect of COSs on pancreatic islet cells was detected under optical microscopy and with colorimetric assay and gel electrophoresis. The activities of glutathione peroxidase and superoxide dismutase, total antioxidant capacity, and content of malondialdehyde in serum and tissue slices of pancreas were examined after 60 d to determine the effect of COSs in streptozotocin-induced diabetes in rats. RESULTS: COSs can prohibit the apoptosis of pancreatic islet cells. All concentrations of COSs can improve the capability of total antioxidant capacity and activity of superoxide dismutase and decrease the content of malondialdehyde drastically. Morphological investigation in the pancreas showed that COSs have resulted in the reduction of islets, loss of pancreatic cells, and nuclear pyknosis of pancreatic cells. CONCLUSION: COSs possess various biological activities and can be used in the treatment of diabetes mellitus.
Asunto(s)
Antioxidantes/farmacología , Quitina/uso terapéutico , Quitosano/farmacología , Diabetes Mellitus Experimental/tratamiento farmacológico , Islotes Pancreáticos/fisiología , Oligosacáridos/uso terapéutico , Animales , Línea Celular , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/patología , Glutatión Peroxidasa/sangre , Células Secretoras de Insulina/efectos de los fármacos , Células Secretoras de Insulina/patología , Islotes Pancreáticos/efectos de los fármacos , Masculino , Malondialdehído/sangre , Metformina/uso terapéutico , Ratones , Ratones Endogámicos NOD , Ratas , Ratas Wistar , Estreptozocina/farmacología , Superóxido Dismutasa/sangreRESUMEN
Two new natural products, tenelate A (1) and B (2), together with the known compound, tenellic acid C (3), were isolated from the mangrove endophytic fungus Talaromyces sp. (SBE-14), from the South China Sea. Their structures were elucidated by spectroscopic methods, mainly 1D and 2D NMR techniques.
Asunto(s)
Benzoatos/química , Éteres Fenílicos/química , Rhizophoraceae/microbiología , Talaromyces/química , Medios de Cultivo/análisis , Fermentación , Espectroscopía de Resonancia Magnética , Espectrometría de Masa por Ionización de Electrospray , Espectrofotometría Infrarroja , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
One new compound 6-demethylvermistatin (1), together with two known compounds, the penicillide derivatives (2) and (3) were isolated from the mangrove fungus Guignardia sp. No. 4382 obtained from the South China Sea. Their structures were assigned using high-resolution electron ionization mass spectrometry(HREIMS), (1)H and (13)C NMR spectra, DEPT, and by 2D COSY, HMQC, and HMBC experiments. The absolute configuration of 1 was established by comparison of its CD with that of vermistatin.
Asunto(s)
Ascomicetos/química , Compuestos Heterocíclicos con 3 Anillos/aislamiento & purificación , Resonancia Magnética Nuclear Biomolecular , Pironas/aislamiento & purificación , Rhizophoraceae/microbiología , Ascomicetos/crecimiento & desarrollo , Isótopos de Carbono , China , Compuestos Heterocíclicos con 3 Anillos/química , Estructura Molecular , Océanos y Mares , Corteza de la Planta/química , Protones , Pironas/químicaRESUMEN
A novel nitro-phenyl glucoside (1) was isolated from mangrove endophytic fungus (fungus B60), collected from the Shenzhen mangrove Acanthus ilicifolius linn. Four related nitro-phenyl compounds (2-5) were also obtained, which were isolated for the first time as natural products. Their structures were established on the basis of NMR spectroscopic, mass spectrometric data and some chemical transformations. In the preliminary bioassay, compound 1 had a slight inhibitory effect on alpha-glucosidase with an IC(50) of 160.3 microM.
Asunto(s)
Hongos/química , Glucósidos/aislamiento & purificación , Rhizophoraceae/microbiología , Glucósidos/química , Espectroscopía de Resonancia Magnética , Espectrofotometría UltravioletaRESUMEN
Anthracenedione derivatives are potent cytotoxic agents to tumor cells. In this study, we investigated the anticancer activities of anthracenedione derivative 1403P-3 separated from the secondary metabolites of the mangrove endophytic fungus No. 1403. Our results demonstrated that 1403P-3 showed potent cytotoxicity not only to human epidermoid carcinoma drug-sensitive parental KB cells but also to multidrug resistant (MDR) KBv200 cells and the IC50 values were 19.66 and 19.27 muM, respectively. Further research indicated that 1403P-3 induced apoptosis in KB cells and KBv200 cells confirmed by Hoechst 33258 staining, detection of DNA fragmentation and cleavage of poly (ADP-ribose) polymerase (PARP). Furthermore, apoptosis triggered by 1403P-3 was characterized by the loss of mitochondrial membrane potential (DeltaPsi(m)), release of cytochrome c, cleavage of Bid, and activation of caspases-2, -3, -7, -8 and -9. Z-IETD-FMK, caspase-8 inhibitor could inhibit the activation of caspase-2 and cleavage of Bid induced by 1403P-3. However, activation of caspase-9 and cleavage of PARP caused by 1403P-3 were not inhibited by Z-IETD-FMK. Additionally, 1403P-3 did not influence the expression level of Bcl-2 and Bax. It is noteworthy that 1403P-3 decreased the generation of reactive oxygen species (ROS) in KB cells and KBv200 cells. DNA binding assay exhibited that apoptosis induced by 1403P-3 was not involved in intercalating to DNA. In summary, 1403P-3 induced apoptosis of KB cells and KBv200 cells through mitochondrial pathway and death receptor pathway. Furthermore, the mitochondrial pathway was independent of reactive oxygen species and activation of caspase-8.
Asunto(s)
Antraquinonas/química , Mitocondrias/metabolismo , Especies Reactivas de Oxígeno , Receptores de Muerte Celular/metabolismo , Antraquinonas/farmacología , Apoptosis , Proteína Proapoptótica que Interacciona Mediante Dominios BH3/metabolismo , Caspasas/metabolismo , Línea Celular Tumoral , Supervivencia Celular , Fragmentación del ADN , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/farmacología , Humanos , Potenciales de la Membrana , Modelos BiológicosRESUMEN
We report the unambiguous assignments of the (1)H and (13)C NMR spectra of two new natural products, namely, 1,4,5,6,7,9-hexahydroxy-2-methoxy-7-methyl-5beta,9beta,8abeta, 6alpha,10aalpha-hexahydroanthracen-10 (10aH)-one (1) and 1,4,6-trihydroxy-2-methoxy-7-methylanthracene-9, 10-dione (2), together with three known anthraquinones. These compounds were all isolated from the marine endophytic fungus No. 1403 collected from the South China Sea. Compounds 3 and 4 were isolated from the marine fungus for the first time. The structures were elucidated by the spectroscopic methods 1D and 2D NMR including COSY, HMQC, HMBC and NOE, and HREIMS. In our cytotoxicity assays, compound 5 showed cytotoxicity toward KB and KBv-200 cells with IC(50) of 1.40 and 2.58 microg/ml, respectively. In addition, the plausible biogenic relationship of compounds 1, 2, 3 and 4 is discussed.