RESUMO
Six new (1-6) and seven known depsidones (7-13) were isolated from the culture of an ant (Monomorium chinensis)-derived fungus Spiromastix sp. MY-1. Their structures were elucidated by extensive spectroscopic analysis including high resolution MS, 1D and 2D NMR data. The new bromide depsidones were obtained through supplementing potassium bromide in the fermentation medium of Spiromastix sp. MY-1. All isolated compounds showed various bioactivities against the tested phytopathogenic bacteria. Particularly, new bromide compound 4, named spiromastixone S, exhibited the strongest activity against Xanthomonas oryzae pv. oryzae with a MIC value of 5.2 µmol·-1.
Assuntos
Formigas , Brometos , Animais , Antibacterianos , Depsídeos , Fungos , Lactonas , Testes de Sensibilidade Microbiana , Estrutura MolecularRESUMO
Two new 2-carboxymethyl-3-hexyl-maleic anhydride derivatives, arthrianhydride A (1) and B (2), along with three known compounds 3-5, were isolated from the fermentation broth of a grasshopper-associated fungus Arthrinium sp. NF2410. The structures of new compounds 1 and 2 were determined based on the analysis of the HR-ESI-MS and NMR spectroscopic data. Furthermore, compounds 1 and 2 were evaluated on inhibitory activity against the enzyme SHP2 and both of them showed moderate inhibitory activity against SHP2.
Assuntos
Anidridos/farmacologia , Inibidores Enzimáticos/farmacologia , Fungos/química , Gafanhotos/microbiologia , Anidridos/isolamento & purificação , Animais , Produtos Biológicos/isolamento & purificação , Produtos Biológicos/farmacologia , Inibidores Enzimáticos/isolamento & purificação , Estrutura Molecular , Proteína Tirosina Fosfatase não Receptora Tipo 11/antagonistas & inibidores , Metabolismo SecundárioRESUMO
A novel lactone-type norcucurbitacin, designated as neocucurbitacin D (1), together with five known cucurbitane triterpenes were isolated from traditional Tibetan medicine "Se Ji Mei Duo", which is the seed of Herpetospermum pedunculosum (Ser.) C.B. Clarke. The structure of neocucurbitacin D was elucidated by spectroscopic analysis, including 2D NMR and X-ray techniques. Compounds 1-6 were screened for their xanthine oxidase (XOD) inhibitory activity. Compound 1, 2 and 4 exhibited significant XOD inhibition with IC50 values ranging from 10.16 to 18.41 µM. The absolute stereochemistry and XOD inhibitiory activity of lactone-type norcucurbitacins was reported firstly.
Assuntos
Cucurbitaceae/química , Inibidores Enzimáticos/isolamento & purificação , Triterpenos/farmacologia , Xantina Oxidase/antagonistas & inibidores , Cucurbitacinas , Inibidores Enzimáticos/farmacologia , Glicosídeos , Humanos , Concentração Inibidora 50 , Lactonas/química , Lactonas/isolamento & purificação , Lactonas/farmacologia , Conformação Molecular , Sementes/química , Triterpenos/isolamento & purificaçãoRESUMO
Three new phenazine-type compounds, named phenazines SA-SC (1-3), together with four new natural products (4-7), were isolated from the fermentation broth of an earwig-associated Streptomyces sp. NA04227. The structures of these compounds were determined by extensive analyses of NMR, high resolution mass spectroscopic data, as well as single-crystal X-ray diffraction measurement. Sequencing and analysis of the genome data allowed us to identify the gene cluster (spz) and propose a biosynthetic pathway for these phenazine-type compounds. Additionally, compounds 1-5 exhibited moderate inhibitory activity against acetylcholinesterase (AChE), and compound 3 showed antimicrobial activities against Micrococcus luteus.
Assuntos
Antibacterianos/química , Insetos/microbiologia , Fenazinas/química , Streptomyces/química , Animais , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Cristalografia por Raios X , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Micrococcus luteus/efeitos dos fármacos , Estrutura Molecular , Família Multigênica , Fenazinas/metabolismo , Fenazinas/farmacologia , Streptomyces/genética , Streptomyces/metabolismoRESUMO
Replacement of the native promoter of theglobal regulator LaeA-like gene of Daldinia eschscholzii by a strong gpdA promoter led to the generation of two novel cyclopentenone metabolites, named dalestones A and B, whose structures were assigned by a combination of spectroscopic analysis, modified Mosher's reaction, and electronic circular dichroism (ECD). Dalestones A and B inhibit the gene expression of TNF-α and IL-6 in LPS-induced RAW264.7 macrophages.
Assuntos
Anti-Inflamatórios/farmacologia , Ciclopentanos/farmacologia , Proteínas Fúngicas/genética , Regiões Promotoras Genéticas/genética , Fatores de Transcrição/genética , Xylariales/química , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/metabolismo , Ciclopentanos/química , Ciclopentanos/isolamento & purificação , Ciclopentanos/metabolismo , Proteínas Fúngicas/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Estrutura Molecular , Células RAW 264.7 , Fatores de Transcrição/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Xylariales/genética , Xylariales/metabolismoRESUMO
Herpecaudin (3), a xanthine oxidase inhibitor with an unprecedented scaffold, was discovered from Herpetospermum caudigerum seeds. The structure was determined by spectroscopic and X-ray single crystallographic methods. A possible biogenetic pathway leading to herpecaudin is proposed, starting from congeners 23,24-dihydrocucurbitacin E (1) and endecaphyllacin B (2), and involving retro-aldol cleavage as a key step. All three compounds proved to be active and represent new scaffolds of non-purine analogue xanthine oxidase inhibitors.
Assuntos
Cucurbitaceae/química , Inibidores Enzimáticos/isolamento & purificação , Terpenos/isolamento & purificação , Xantina Oxidase/antagonistas & inibidores , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores Enzimáticos/farmacologia , Humanos , Estrutura Molecular , Terpenos/química , Terpenos/farmacologiaRESUMO
Dalesconols (dalesconols A and B) are novel polyketides with strong immunosuppressive activity produced by Daldinia eschscholzii. In this work, the effects of different media (M1, M2, and M3) on fungus growth and dalesconols biosynthesis were firstly tested and compared. Intermediates and enzyme analysis indicated that laccase had the major contribution to dalesconols biosynthesis. The key role of laccase on dalesconols biosynthesis was further experimentally confirmed, which suggested that the modified M2 was more favored for laccase and dalesconols production. Thereafter, the medium composition was optimized by RSM with a fermentation titer of 36.66 mg/L obtained. Furthermore, Ca(2+) induction was employed to up-regulate of laccase activity and further enhanced dalesconols production (76.90 mg/L), which was 308% higher than that in M2. In addition, dalesconols production reached 63.42 mg/L in scale-up experiments. This work indicated great potential of laccase as a key enzyme on regulation of dalesconols production.
Assuntos
Microbiologia Industrial/métodos , Lacase/metabolismo , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , Xylariales/metabolismo , Reatores Biológicos , Cálcio/metabolismo , Carbono/metabolismo , Meios de Cultura/química , Meios de Cultura/farmacologia , Fermentação , Microbiologia Industrial/instrumentação , Nitrogênio/metabolismo , Regulação para Cima , Xylariales/efeitos dos fármacos , Xylariales/crescimento & desenvolvimentoRESUMO
In this work, the separation and purification of fumigaclavine C (FC), an ergot alkaloid with strong anti-inflammatory activity from fermented mycelia of Aspergillus fumigatus was systematically evaluated. Among the eight tested resins, the non-polar resin D101 displayed the best adsorption and desorption based on of static adsorption and desorption tests. Adsorption isotherms were constructed on D101 resin and fitted well to the Freundlich model. Dynamic adsorption and desorption tests on a column packed with D101 resin have been investigated for optimization of chromatographic parameters. Under optimized conditions, the contents of FC increased from 7.32% (w/w) in the crude extract to 67.54% in the final product with a recovery yield of 90.35% (w/w) via one run. Furthermore, a lab scale-up separation was carried out, in which the FC content and recovery yield were 65.83% and 90.13%, respectively. These results demonstrated that this adsorption-desorption strategy by using D101 resin was simple and efficient, thus showing potential for large scale purification and preparation of FC in the future.
Assuntos
Aspergillus fumigatus/metabolismo , Cromoterapia/métodos , Alcaloides de Claviceps/isolamento & purificação , Alcaloides Indólicos/isolamento & purificação , Micélio/química , Resinas Sintéticas/química , Adsorção , Aspergillus fumigatus/química , Cromoterapia/instrumentação , Alcaloides de Claviceps/metabolismo , Fermentação , Alcaloides Indólicos/metabolismo , Micélio/metabolismo , PorosidadeRESUMO
Phytochemical investigation of the stem wood of Dipterocarpus alatus led to the isolation and characterization of four new oligostilbenoids, dipterocarpols A-D (1-4), together with two known resveratrol oligomers, hopeahainol (5) and hopeafuran (6). The structures of the new compounds were determined by comprehensive spectral analysis including 1D and 2D NMR, and high-resolution MS. The absolute configurations were determined by NOESY and CD spectra. Dipterocarpol A (1) and hopeahainol A (5) showed moderate acetylcholinesterase inhibitory activity with IC50 values of 8.28 µM and 11.28 µM, respectively. Furthermore, the discovery of compound 3 gave the first evidence that the biosynthetic origin of resveratrol aneuploids is related to the loss of a half resveratrol unit by oxidative cleavage.
Assuntos
Inibidores da Colinesterase/química , Dipterocarpaceae/química , Estilbenos/química , Inibidores da Colinesterase/isolamento & purificação , Inibidores da Colinesterase/farmacologia , Ressonância Magnética Nuclear Biomolecular , Resveratrol , Estilbenos/isolamento & purificação , Estilbenos/farmacologiaRESUMO
Five new flavonoids, cryptoconones A-E (1-5), along with six known compounds (6-11), were isolated from the stems of Cryptocarya concinna. The structures of these compounds were elucidated on the basis of spectroscopic data interpretation, and the absolute configurations were determined via circular dichroism spectra and X-ray crystal analysis. The cytotoxic and antimicrobial activities of these compounds were also evaluated. Compounds 9 and 10 exhibited moderate cytotoxic activities against HCT116, HT-29, SW480, and MDA-MB-231 cell lines with IC50 values ranging from 6.25 to 9.35 µM. Compounds 8 and 11 exhibited antimicrobial activity against Fusarium moniliforme and Botrytis cinerea, respectively, with the same minimum inhibitory concentration of 5 µg/mL.
Assuntos
Anti-Infecciosos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Cryptocarya/química , Flavonoides/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Botrytis/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cristalografia por Raios X , Ensaios de Seleção de Medicamentos Antitumorais , Flavonoides/química , Flavonoides/isolamento & purificação , Fusarium/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Estrutura Molecular , Caules de Planta/químicaRESUMO
One new flavonol, chlorflavonin A (1), four new diterpenoids, aspergiloids E-H (3, 5-7), together with eight known compounds (2, 4, 8-13) were isolated from solid fermentation of Aspergillus sp. (strain no. YXf3), an endophytic fungus from Ginkgo biloba. Their structures were determined through detailed spectroscopic analysis combined with comparison of NMR spectra data with reported ones. All of them were screened on cytotoxicity against KB, SGC-7901, SW1116, and A549 cell lines; compounds 4, 9-11 exhibited moderate activities with IC50 values ranging from 6.74 to 46.64 µM.
Assuntos
Antineoplásicos/análise , Aspergillus/química , Diterpenos/isolamento & purificação , Flavonóis/isolamento & purificação , Linhagem Celular Tumoral , Cromatografia Líquida de Alta Pressão , Diterpenos/química , Ensaios de Seleção de Medicamentos Antitumorais , Endófitos/química , Flavonóis/química , Ginkgo biloba/microbiologia , Humanos , Estrutura MolecularRESUMO
Chemical investigation of the insect-derived actinomycete Amycolatopsis sp. HCa1 with NMR-guided fractionation led to the isolation of eight new tetrasaccharide derivatives containing an unusual nonreducing glucotetraose skeleton, named actinotetraoses A-H (1-8), and one known compound, tigloside (9). The structures of these compounds were determined on the basis of analyses of their spectroscopic data. The in vitro immunosuppressive activity and cytotoxicity of these compounds were evaluated by T cell viability and MTT assays, respectively. Only actinotetraose E (5) displayed weak immunosuppressive activity.
Assuntos
Actinobacteria/química , Gafanhotos/microbiologia , Imunossupressores/isolamento & purificação , Oligossacarídeos/isolamento & purificação , Linfócitos T/efeitos dos fármacos , Actinobacteria/isolamento & purificação , Animais , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Fermentação , Células HeLa , Células Hep G2 , Humanos , Imunossupressores/química , Imunossupressores/farmacologia , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Micélio/química , Oligossacarídeos/química , Oligossacarídeos/farmacologia , Rotação OcularRESUMO
Two new alkaloids chaetoglobosins V (1) and W (2), together with the six known congeners 3-8, were isolated through bioassay-guided fractionations from the EtOAc extract of a solid culture of Chaetomium globosum IFB-E041. The structures were elucidated by spectroscopic methods including mainly 1D and 2D NMR techniques. Chaetoglobosin W (2) was unique in its possession of an oxolane ring formed via an oxygen bridge between C-3 and C-6. The isolated fungal metabolites exhibited moderate cytotoxic activities against four human cancer cell lines (KB, K562, MCF-7, and HepG2) with their IC(50) values in a range of 18-30 µg/mL.
Assuntos
Antineoplásicos/uso terapêutico , Produtos Biológicos/uso terapêutico , Chaetomium/química , Alcaloides Indólicos/uso terapêutico , Neoplasias/tratamento farmacológico , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Artemisia annua/microbiologia , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Linhagem Celular Tumoral , Humanos , Alcaloides Indólicos/isolamento & purificação , Alcaloides Indólicos/farmacologiaRESUMO
(1)H-NMR guided fractionation of the EtOAc extract from the culture of Myrothecium gramminum (strain no. 3.1968) led to the isolation of eight cytotoxic trichothecene macrolides ( 1 - 8), all being substantially inhibitory against HepG2 (human hepatocellular carcinoma) and KB (human nasopharynyeal epidermoid tumor) cell lines with IC (50) values ranging from 2.2 to 12.2 mug/mL. Their inactivity to or weaker action on Vero cells (IC (50) values > 20 microg/mL, originated from the African green monkey kidney) highlighted preliminarily the nature of the selective cytotoxicity of the fungal metabolites against the test cancer cell lines. In addition, verrucarin A ( 1) and roridin A ( 5) were found to be potent inhibitors of the radial growth of Echinochloa crusgalli with corresponding IC (50) values of (7.96 +/- 0.31) x 10 ( - 6) and (9.18 +/- 0.44) x 10 ( - 6) M, respectively, which were more potent than that of the positive control (2,4-dichlorophenoxyacetic acid) [(9.40 +/- 0.04) x 10 ( - 5) M].