RESUMO
Nine new naphthacemycins (1-9), along with one known naphthacemycin (10) were isolated from the culture of Streptomyces sp. N12W1565. Their structures were elucidated on the basis of spectroscopic analysis, including UV, NMR, and HRESIMS. All the compounds showed significant activity, with IC50 values less than 10 µM against protein-tyrosine phosphatase 1B (PTP1B). The anti-PTP1B structure-activity relationship of naphthacemycins (1-10) is discussed. These findings provide a promising starting point for the development of naphthacemycins as potential anti-PTP1B agents.
Assuntos
Inibidores Enzimáticos/farmacologia , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Streptomyces/química , Inibidores Enzimáticos/química , Fermentação , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Espectrometria de Massas por Ionização por Electrospray , Espectrofotometria Ultravioleta , Relação Estrutura-AtividadeRESUMO
The marine mangrove Xylocarpus granatum is used as a folk medicine and is rich in bioactive limonoids. The quantitative determination of the chemical composition and distribution of limonoids in different parts of X. granatum fruit (fruit peel, seed coat, seed kernels, seed, and fruit) is significant for authentication and quality control purposes. However, the quantitative determination of limonoids in X. granatum has not yet been reported. In this study, a chemometric-assisted liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of 17 limonoids to reveal the chemical composition and distribution in different parts of X. granatum fruit. Ultrasonic-assisted extraction, optimized by response surface methodology (RSM), was more accurate than the general one-variable-at-a-time method. The overall distribution of 17 limonoids in different parts of X. granatum fruit had the following order: seed kernels > seed > fruit, and 13 limonoids showed a rank order of seed kernels > seed > fruit > fruit peel > seed coat. Furthermore, principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to analyze the LC-MS/MS data and provide a chemometric model for easy visualization and interpretation to classify the different parts of X. granatum fruit. In addition, the study indicated that the chemometric-assisted strategy, consisting of RSM, PCA, and OPLS-DA for the development, optimization, and data analysis of multicomponent quantitation by LC-MS/MS, is effective and feasible. This study provided the chemical composition and distribution evidence for the authentication and quality control of X. granatum fruit.
Assuntos
Cromatografia Líquida/métodos , Limoninas/análise , Meliaceae/química , Estruturas Vegetais/química , Espectrometria de Massas em Tandem/métodos , Análise de Componente PrincipalRESUMO
Two new limonoids, named xylomexicanins C and D, were isolated from a dichloromethane extract of the seeds of Xylocarpus granatum cultivated in Hainan, China, and their structures were elucidated on the basis of one- and two-dimensional NMR (including 1H, 13C-NMR, DEPT, 1H-1H COSY, HSQC, HMBC, and NOESY) and confirmed by high-resolution mass spectrometry. Xylomexicanin C exhibited antiproliferative activity against human breast carcinoma cells (KT).
Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Limoninas/química , Limoninas/farmacologia , Meliaceae/química , Antineoplásicos/isolamento & purificação , Linhagem Celular Tumoral , Humanos , Limoninas/isolamento & purificaçãoRESUMO
OBJECTIVE: To study the chemical constituents in the needles of Taxus cuspidata collected from Japan. METHODS: Chemical constituents were isolated by column chromatography, TLC and preparative HPLC. The structures were identified on the basis of NMR spectral analysis. RESULTS: Six non-taxoids were isolated and identified as: 4-[(1E)-3-hydroxy-1-buten-1-yl]-3,5,5-trimethyl-2-cyclohexen-1-one (1), megastigm-5-ene-3, 9-diol (2), 6alpha-epoxy-7-megastigmen-9-one (3), 4-(4-hydroxyphenyl)-2-butanone (4), 12-hydroxy-alpha-cyperone (5), scutellarein-7-O-alpha-L-rhamnoside (6). CONCLUSION: Compounds 2 - 6 are isolated from Taxus genus for the first time. Compound 1 is obtained from Taxus cuspidata for the first time.
Assuntos
Taxus/química , Cromatografia Líquida de Alta Pressão , Espectroscopia de Ressonância Magnética , Extratos Vegetais/química , TaxoidesRESUMO
A phytochemical investigation of Chromolaena odorata resulted in the isolation of five new compounds, 5aα,6,9,9aß,10-pentahydro-10ß-hydroxy-7-methylanthra[1,2-d][1,3]dioxol-5-one (1), 1,2-methylenedioxy-6-methylanthraquinone (2), 3-hydroxy-1,2,4-trimethoxy-6-methylanthraquinone (3), 3-hydroxy-1,2-dimethoxy-6-methylanthraquinone (4), and 7-methoxy-7-epi-medioresinol (5), together with 12 known compounds, odoratin (6), 3ß-acetyloleanolic acid (7), ursolic acid (8), ombuin (9), 4,2'-dihydroxy-4',5',6'-trimethoxychalcone (10), (-)-pinoresinol (11), austrocortinin (12), tianshic acid (13), cleomiscosin D (14), (-)-medioresinol (15), (-)-syringaresinol (16), and cleomiscosin A (17). All the compounds were evaluated for their PPARγ transactivation activity, and compound 6 showed moderate activity with an EC(50) value of 3.10 µM.
Assuntos
Antraquinonas/isolamento & purificação , Chromolaena/química , Dioxóis/isolamento & purificação , Dioxóis/farmacologia , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Lignanas/isolamento & purificação , Lignanas/farmacologia , PPAR gama/agonistas , Antraquinonas/química , Antraquinonas/farmacologia , Dioxóis/química , Medicamentos de Ervas Chinesas/química , Flavonoides/química , Furanos/química , Furanos/isolamento & purificação , Hepatócitos/efeitos dos fármacos , Humanos , Lignanas/química , Luciferases/metabolismo , Estrutura Molecular , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/farmacologia , EstereoisomerismoRESUMO
Eight sesquiterpene lactones were isolated from the roots of Inula helenium and flowers of I. japonica. Among them, isoalantolactone (3) and santamarine (6) exhibited significant growth inhibitory activities against gynecologic cancer cell lines, while others weakly inhibited the growth of the cell lines (IC50 < or = 100 microM). In addition, 3 significantly inhibited the tumour growth of S180 tumour-bearing mice. Compounds 3 and 6 were not toxic to human embryonic lung fibroblast cells in vitro. These results demonstrated that the antitumour activities are closely related to the structures of the compounds, that is, an alpha-exomethylene-gamma-lactone ring is necessary for these activities.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Inula/química , Lactonas/farmacologia , Sesquiterpenos/química , Linhagem Celular Tumoral , HumanosRESUMO
Seven undescribed sesquiterpene lactone dimers (SLDs) (carpeabrodilactones A-G), one known SLD, and six known sesquiterpenes were isolated from the fruit of Carpesium abrotanoides L. Carpeabrodilactone A was a dimeric carabrane featuring a rare C-13-C-13' linkage. Carpeabrodilactones B and C are the first two SLDs to be described possessing a carabranolide unit and a guaianolide unit connected by an O-ether linkage. The structures of the SLDs were assigned based on HRESIMS, NMR analysis, 13C NMR calculation, ECD calculation, and modified Mosher's method. Four SLDs showed potent cytotoxicity against K562 and/or A549 cells, with IC50 values below 10 µM, but none inhibited protein tyrosine phosphatases at 40 µM, including PTP1B, SHP1, CD45, and TCPTP.
Assuntos
Asteraceae , Sesquiterpenos , Asteraceae/química , Éteres , Frutas , Lactonas/química , Lactonas/farmacologia , Estrutura Molecular , Compostos Fitoquímicos , Sesquiterpenos/química , Sesquiterpenos/farmacologiaRESUMO
Five unprecedented chromone derivatives involving a 6/6/5/5/5/6 hexacyclic scaffold (1, 2), 6/6/5/6/6/6/6 heptacyclic scaffold (3), and 6/6/6/5/5/6 hexacyclic scaffold (4, 5) were obtained from the fungus Aspergillus deflectus NCC0415. Their structures were identified using comprehensive spectroscopic analysis, single-crystal X-ray diffraction, and electronic circular dichroism calculations. Except for 3, the other compounds, especially the 6/6/6/5/5/6 hexacyclic derivatives (4 and 5), exhibited potent inosine-5'-monophosphate dehydrogenase (IMPDH) inhibitory activities.
Assuntos
AspergillusRESUMO
Achillinin A (2ß,3ß-epoxy-1α,4ß,10α-trihydroxyguai-11(13)-en-12,6α-olide, 1), a new guaianolide isolated from the flower of Achillea millefolium, exhibited potential antiproliferative activity to A549, RERF-LC-kj and QG-90 cells with 50% inhibitory concentration (IC(50)) values of 5.8, 10 and 0.31 µM, respectively.
Assuntos
Achillea/química , Adenocarcinoma/tratamento farmacológico , Antineoplásicos Fitogênicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Fitoterapia , Extratos Vegetais/farmacologia , Sesquiterpenos/farmacologia , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Adenocarcinoma/patologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Flores/química , Humanos , Concentração Inibidora 50 , Neoplasias Pulmonares/patologia , Espectroscopia de Ressonância Magnética , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Sesquiterpenos/química , Sesquiterpenos/uso terapêutico , Carcinoma de Pequenas Células do Pulmão/patologiaRESUMO
A novel 6/8/6-membered taxane with a rare C-12(13)-double bond and rare 2(3â20)abeotaxane were isolated from the needles of Taxus canadensis. Their structures were characterized as 7ß,9α,10ß-triacetoxytaxa-4(20),12-diene-2α,5α,11ß-triol (1) and 2α,7ß,10ß-triacetoxy-5α-hydroxy-2(3â20)abeotaxa-4(20),11-diene-9,13-dione (2) on the basis of 1D and 2D spectroscopic data. 1 is the first example of a natural taxane without substitution at both C-13 and C-14.
Assuntos
Antineoplásicos/análise , Extratos Vegetais/análise , Taxoides/análise , Taxus/química , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Feminino , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Folhas de Planta/química , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Taxoides/química , Taxoides/isolamento & purificação , Taxoides/farmacologia , Falha de Tratamento , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/patologiaRESUMO
Three new taxanes, 2 α,9 α,10 ß-triacetoxy-13 α-( ß-D-glucopyranosyloxy)taxa-4(20),11-dien-5 α-ol, 5 α,10 ß,13 α-triacetoxytax-11-ene-2 α,7 ß,9 α,20-tetraol, and 5 α,10 ß,13 ß-triacetoxy-2 α,7 ß-dihydroxy-2(3â20) abeotaxa-4(20),11-dien-9-one, were isolated from the leaves of the Japanese yew, Taxus cuspidata. Compound 1 is the first example of a taxane with 13-glycosidic linkage.
Assuntos
Glucosídeos/isolamento & purificação , Extratos Vegetais , Taxoides/isolamento & purificação , Taxus/química , Glucosídeos/química , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Folhas de Planta , Taxoides/químicaRESUMO
Ocean is a unique and excellent resource that provides a diverse array of intriguing natural products. Marine natural products have demonstrated significant and extremely potent biological activities and have captured the attention of natural products chemists in the past few decades. It is increasingly recognized that a wealth of fascinating natural products and novel chemical entities will play a dominant role in the discovery of useful leads for the development of pharmaceutical agents and provide useful probes to lead to breakthroughs in a variety of life-science fields. This article focused on the research progress of chemistry of marine natural products in recent five years.
Assuntos
Organismos Aquáticos/química , Produtos Biológicos/isolamento & purificação , Biologia Marinha , Alcaloides/química , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Animais , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Anti-Infecciosos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Humanos , Macrolídeos/química , Macrolídeos/isolamento & purificação , Macrolídeos/farmacologia , Toxinas Marinhas/química , Toxinas Marinhas/isolamento & purificação , Toxinas Marinhas/farmacologia , Estrutura Molecular , Peptídeos/química , Peptídeos/isolamento & purificação , Peptídeos/farmacologia , Esteroides/química , Esteroides/isolamento & purificação , Esteroides/farmacologia , Terpenos/química , Terpenos/isolamento & purificação , Terpenos/farmacologiaRESUMO
OBJECTIVE: To investigate the microbiological transformation of paeoniflorin and albiflorin. METHOD: The bacteria strains able to transform paeoniflorin and albiflorin were screened from 18 strains of microorganisms. The products were isolated by chromatography method and their structures were elucidated by spectral technology. RESULT: It was found that Cunninghamella blakesleana (AS 3.970) and Syncephalastrum racemosum (AS 3.264) could convert paeoniflorin and albiflorin efficiently, respectively. C. blakesleana could convert paeoniflorin to produce albiflorin, while S. racemosum could convert albiflorin to produce paeoniflorin. CONCLUSION: Paeoniflorin and albiflorin could be converted each other in definited condition.
Assuntos
Benzoatos/metabolismo , Hidrocarbonetos Aromáticos com Pontes/metabolismo , Cunninghamella/metabolismo , Glucosídeos/metabolismo , Mucorales/metabolismo , Biotransformação , MonoterpenosRESUMO
Six undescribed azaphilones, deflectins C1-C3, deflectins D1-D2, and deflectin E, along with five known azaphilones were obtained from a solid culture of the wild fungus Aspergillus deflectus NCC0415. Their structures were determined by HRESIMS, NMR and ECD analyses, together with the GIAO 13C NMR calculation method. All compounds displayed strong or moderate inhibitory activity against protein tyrosine phosphatases SHP2 and PTP1B. Structure-activity relationship analysis of these azaphilones suggested that the length of the ketone aliphatic side chain would affect their SHP2 and PTP1B inhibitory activity. In addition, the presence of a Δ8(12) double bond on γ-lactone ring and the presence of CH3-2' in fatty chains may increase their inhibitory activity.
Assuntos
Aspergillus/química , Benzopiranos/farmacologia , Inibidores Enzimáticos/farmacologia , Compostos Fitoquímicos/farmacologia , Pigmentos Biológicos/farmacologia , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Benzopiranos/química , Benzopiranos/isolamento & purificação , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Humanos , Estrutura Molecular , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Pigmentos Biológicos/química , Pigmentos Biológicos/isolamento & purificação , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Relação Estrutura-AtividadeRESUMO
Taxusecone, 2alpha,7beta,9alpha,10beta-tetraacetoxy-5alpha,12-dihydroxy-11,12-secotax-4(20)-ene-11,13-dione (1), a novel taxane with an unprecedented skeleton, was isolated from the needles of Taxus cuspidata.
Assuntos
Taxoides/química , Taxoides/isolamento & purificação , Taxus/química , Taxus/anatomia & histologia , Taxus/metabolismoRESUMO
The plants of genus Celastrus, distributed in Asia, have been used as natural insecticides and folk medicines to treat fever, chill, joint pain, edema, rheumatoid arthritis, and bacterial infection in China for a long time. This contribution reviews the chemical constituents, isolated from the plants in genus Celastrus in the past few decades, and their biological activities. The compounds listed are sesquiterpenes (beta-agarofurans), diterpenes, triterpenes, alkaloids, and flavonoids.
Assuntos
Celastrus/química , Alcaloides/química , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Diterpenos/química , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Flavonoides/química , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Medicina Tradicional Chinesa , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/farmacologia , Triterpenos/química , Triterpenos/isolamento & purificação , Triterpenos/farmacologiaRESUMO
Two new mexicanolide-type limonoids, named xylomexicanin A (1) and xylomexicanin B (2), were isolated from seeds of the Chinese mangrove Xylocarpus granatum. Their structures were elucidated on the basis of spectroscopic methods. Compound 1 exhibited antiproliferative activity against human breast carcinoma cells (KT), while 2 did not show inhibitory effects on eleven human tumour cell lines tested.
Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Limoninas/química , Limoninas/farmacologia , Meliaceae/química , Neoplasias/tratamento farmacológico , Sementes/química , Antineoplásicos/isolamento & purificação , Sudeste Asiático , Linhagem Celular Tumoral/efeitos dos fármacos , Feminino , Humanos , Limoninas/isolamento & purificação , Espectroscopia de Ressonância Magnética , Medicina TradicionalRESUMO
Two 11(15-->1)abeotaxanes having a tetrahydrofuran ring along the carbon atoms C-2, C-3, C-4, C-20 were identified for the first time from the needles of the Canadian yew, Taxus canadensis. The compounds could be identified as 4alpha,10beta,13alpha-triacetoxy-15-benzoyloxy-2alpha,20beta-epoxy-11(15-->1)abeotax-11-ene-5alpha,7beta,9alpha-triol (1) and 4alpha,7beta,9alpha,10beta,15-pentaacetoxy-2alpha,20beta-epoxy-11(15-->1)abeotax-11-ene-5alpha,13alpha-diol (2) on the basis of 1D-, 2D-NMR evidence and high-resolution FABMS analysis. Compound 1 showed weak growth inhibitory activities against T-98 and MM1-CB cells in vitro.
Assuntos
Linhagem Celular Tumoral/efeitos dos fármacos , Compostos de Epóxi/química , Células HeLa/efeitos dos fármacos , Taxoides/química , Taxus/química , Sobrevivência Celular/efeitos dos fármacos , Compostos de Epóxi/isolamento & purificação , Compostos de Epóxi/farmacologia , Humanos , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Folhas de Planta/química , Taxoides/isolamento & purificação , Taxoides/farmacologiaRESUMO
Poria cocos (Schw.) Wolf (PCW) is a widely used traditional Chinese medicine and dietary supplement. Its four parts including Poriae Cutis (PC), Rubra Poria (RP), White Poria (WP) and Poria cum Radix Pini (PRP) have different pharmacological effects and clinical applications. It is necessary to establish analytical platforms for differentiating the chemical composition of four botanical parts for the rational utilization. We established a simultaneous qualitative and quantitative method based on UHPLC-MS combined metabolomics approach to give an explanation of the distribution of triterpene compounds in four parts. Eight triterpene compounds were determined absolutely and a total of 51 triterpene compounds were tentatively identified in PCW. PC and PRP showed a quite clear discrimination by the principal component analysis (PCA) and orthogonal projections to latent structures-discriminant analysis (OPLS-DA) and twelve differential compounds were found. Four compounds including poricoic acid D, 16α-hydroxydehydrotrametenolic acid, 3-epidehydrotumulosic acid, 25-hydroxypolyporenic acid C were speculated to be related to diuretic effects.
Assuntos
Estudos de Avaliação como Assunto , Metabolômica , Triterpenos/análise , Wolfiporia/química , Cromatografia Líquida de Alta Pressão , Análise Discriminante , Análise Multivariada , Raízes de Plantas/química , Análise de Componente Principal , Reprodutibilidade dos Testes , Espectrometria de Massas em TandemRESUMO
Echinopines A (1) and B (2), novel sesquiterpenoids with an unprecedented rearranged skeleton named echinopane, were isolated from the roots of Echinops spinosus. The structures were elucidated by extensive spectroscopic analysis. The relative configuration of 1 was assigned by a combination of NOESY correlations and a simulation analysis. A plausible biosynthetic pathway for echinopane was discussed.