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1.
J Chem Phys ; 151(12): 125103, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31575200

RESUMO

This article reports on a frequency domain analysis of quasielastic neutron scattering spectra from free and Huperzine-A-inhibited human acetylcholinesterase, extending a recent time domain analysis of the same experimental data [M. Saouessi et al., J. Chem. Phys. 150, 161104 (2019)]. An important technical point here is the construction of a semianalytical model for the resolution-broadened dynamic structure factor that can be fitted to the experimental spectra. We find comparable parameters as in our previous study and demonstrate that our model is sensitive to subpercent changes in the experimental data, which are caused by reversible binding of the inhibitor Huperzine A.


Assuntos
Acetilcolinesterase/química , Alcaloides/química , Inibidores da Colinesterase/química , Sesquiterpenos/química , Alcaloides/farmacologia , Inibidores da Colinesterase/farmacologia , Humanos , Difração de Nêutrons , Domínios Proteicos , Sesquiterpenos/farmacologia
2.
J Agric Food Chem ; 67(44): 12182-12190, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31609606

RESUMO

In continuation of our program to develop natural-product-based pesticidal candidates, matrinic/oxymatrinic amides were obtained through structural optimization of matrine. N'-(4-Fluoro)phenyl-N-(4-bromo)phenylsulfonyloxymatrinic amide (IIm) showed potent insecticidal activity against Mythimna separata. N-(Un)substituted phenylsulfonylmatrinic acids (3a-c) exhibited promising acaricidal activity against Tetranychus cinnabarinus. By qRT-PCR analysis of nAChR subunits and AChE genes and determination of AChE activity of (un)treated T. cinnabarinus, it suggested that the open lactam ring of matrine and carboxyl group and (4-methyl)phenylsulfonyl of N-(4-methyl)phenylsulfonylmatrinic acid (3b) were necessary for action with α2, α4, α5, and ß3 nAChR subunits; compound 3b was an inhibitor of AChE in T. cinnabarinus, and AChE was one possible target of action in T. cinnabarinus against 3b; and compound 3b may be an antagonist of nAChR and AChE in T. cinnabarinus.


Assuntos
Acaricidas/química , Alcaloides/química , Amidas/química , Inseticidas/química , Quinolizinas/química , Acaricidas/síntese química , Acaricidas/farmacologia , Acetilcolinesterase/genética , Acetilcolinesterase/metabolismo , Alcaloides/farmacologia , Amidas/farmacologia , Animais , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/química , Feminino , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Inseticidas/síntese química , Inseticidas/farmacologia , Estrutura Molecular , Mariposas/efeitos dos fármacos , Mariposas/genética , Mariposas/crescimento & desenvolvimento , Mariposas/metabolismo , Quinolizinas/farmacologia , Relação Estrutura-Atividade , Tetranychidae/efeitos dos fármacos , Tetranychidae/genética , Tetranychidae/crescimento & desenvolvimento , Tetranychidae/metabolismo
3.
J Agric Food Chem ; 67(41): 11388-11395, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31536348

RESUMO

Venomous imported fire ants cause significant medical problems. Alkaloids are an important component of imported fire ant venom. Piperidine and piperideine alkaloids have been identified in fire ant venom. In this study, we studied the venom alkaloids of the red imported fire ant, Solenopsis invicta Buren, the black imported fire ant, Solenopsis richteri Forel, and the hybrid, S. invicta × S. richteri. Pyridine alkaloids were detected the first time in fire ants using solid-phase microextraction (SPME) coupled with gas chromatography-mass spectrometry (SPME-GC-MS). The thermal desorption process was manipulated to facilitate the isolation and identification of pyridine alkaloids that were coeluted with piperidine or piperideine alkaloids in GC. After SPME extraction of ant venom, we conducted a series of consecutive GC-MS injections, each with a partial desorption. Hidden pyridine alkaloid peaks were revealed after the overlapping piperidine or piperidiene alkaloid peaks had been desorbed. Using this approach, 10 2-methyl-6-alkyl (or alkenyl)pyridines (1-10) were found the first time in the venom of imported fire ants. Structures of three pyridine alkaloids were confirmed by synthesis, including 2-methyl-6-undecylpyridine (1), 2-methyl-6-tridecylpyridine (7), and 2-methyl-6-pentadecylpyridine (10). We also developed a silica gel column chromatography method to separate the pyridine alkaloids from other alkaloids. Using column chromatography and GC-MS with single ion monitoring at 107 m/z, five pyridine alkaloids were quantified for both workers and female alates of S. invicta and S. richteri.


Assuntos
Alcaloides/química , Venenos de Formiga/química , Formigas/química , Piridinas/química , Alcaloides/isolamento & purificação , Animais , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Estrutura Molecular , Piridinas/isolamento & purificação , Microextração em Fase Sólida
4.
Bol. latinoam. Caribe plantas med. aromát ; 18(5): 527-532, sept. 2019. ilus, tab
Artigo em Inglês | LILACS | ID: biblio-1008292

RESUMO

Chemical constituents and biological activities of the aerial parts of Piper erecticaule C.DC. have been studied for the first time. Fractionation and purification of the extracts afforded aristolactam AII (1), aristolactam BII (2), piperolactam A (3), piperolactam C (4), piperolactam D (5), together with terpenoids of ß-sitosterol, ß-sitostenone, taraxerol, and lupeol. The structures of these compounds were obtained by analysis of their spectroscopic data, as well as the comparison with that of reported data. Acetylcholinesterase inhibitory activity revealed that compounds 1 and 3 showed strong AChE inhibitory effects with the percentage inhibition of 75.8% and 74.8%, respectively.


Se estudiaron por primera vez los constituyentes químicos y actividad biológica de las partes aéreas de Piper erecticaule C.DC. El fraccionamiento y la purificación de los extractos proporcionaron aristolactama AII (1), aristolactama BII (2), piperolactama A (3), piperolactama C (4), piperolactama D (5), junto con terpenoides de ß-sitosterol, ß-sitostenona, taraxerol, y el lupeol. Las estructuras de estos compuestos se obtuvieron mediante el análisis de sus datos espectroscópicos, así como mediante la comparación con datos ya informados. La actividad inhibidora de la acetilcolinesterasa reveló que los compuestos 1 y 3 mostraron un potente efecto inhibidor de la AChE con un porcentaje de inhibición del 75.8% y 74.8%, respectivamente.


Assuntos
Aporfinas/farmacologia , Acetilcolinesterase/efeitos dos fármacos , Extratos Vegetais/química , Inibidores da Colinesterase/farmacologia , Piper/química , Alcaloides/farmacologia , Aporfinas/química , Terpenos , Inibidores da Colinesterase/química , Alcaloides Indólicos/química , Alcaloides/química , Lactamas/química
5.
Fitoterapia ; 137: 104281, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31381957

RESUMO

Veratrum californicum is a rich source of steroidal alkaloids, many of which have proven to be antagonists of the Hedgehog (Hh) signaling pathway that becomes aberrant in over twenty types of cancer. These alkaloids first became known in the 1950's due to their teratogenic properties, which resulted in newborn and fetal lambs developing cyclopia as a result of pregnant ewes consuming Veratrum californicum. It was discovered that the alkaloids in V. californicum were concentrated in the root and rhizome of the plant with much lower amounts of the most active alkaloid, cyclopamine, present in the aerial plant, especially in the late growth season. Inspired by the limitations in analytical instrumentation and methods available to researchers at the time of the original investigation, we have used state-of-the-art instrumentation and modern analytical methods to quantitate four steroidal alkaloids based on study parameters including plant part, harvest location, and growth stage. The results of the current inquiry detail differences in alkaloid composition based on the study parameters, provide a detailed assessment for alkaloids that have been characterized previously (cyclopamine, veratramine, muldamine and isorubijervine), and identify at least six alkaloids that have not been previously characterized. This study provides insight into optimal harvest time, plant growth stage, harvest location, and plant part required to isolate, yet to be characterized, alkaloids of interest for exploration as Hh pathway antagonists with desirable medicinal properties.


Assuntos
Alcaloides/química , Esteroides/química , Veratrum/química , Alcaloides/isolamento & purificação , Proteínas Hedgehog/antagonistas & inibidores , Idaho , Estrutura Molecular , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Componentes Aéreos da Planta/química , Rizoma/química , Estações do Ano , Esteroides/isolamento & purificação , Alcaloides de Veratrum
6.
Oncol Rep ; 42(4): 1451-1458, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31364732

RESUMO

Epithelial­mesenchymal transition (EMT) is closely related to tumor metastasis, and offers insight into novel strategies for cancer treatment. HMQ­T­F2 (F2) is a taspine derivative, which has excellent anticancer activity in human cervical cancer. The present study aimed to evaluate the effect of F2 on in vitro migration of HeLa cells. The present data demonstrated that F2 inhibited migration of HeLa cells by negatively regulating the Wnt signaling pathway and reversing EMT. F2 not only mediated Frizzled8, p­LRP6 and LRP6 expression, but also downregulated the phosphorylation of GSK3ß, and concurrently decreased the nucleus protein expression of MMP2, MMP3, MMP7, MMP9, and c­Myc. In addition, the expression of N­cadherin, vimentin, Snail and HIF­1α were downregulated and that of E­cadherin was upregulated after F2 treatment. F2 was also associated with the downregulation of the PI3K/Akt/mTOR signaling pathways. Notably, F2 induced HeLa cell accumulation at the S phase and cell apoptosis. These results provide evidence that F2 inhibits HeLa cell migration, proliferation and promotes apoptosis. It also reverses EMT, potentially via the PI3K/Akt signaling pathway. Therefore, F2 may be a potential therapeutic reagent against cervical cancer.


Assuntos
Alcaloides/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/metabolismo , Alcaloides/química , Apoptose/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Feminino , Células HeLa , Humanos , Fase S/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Neoplasias do Colo do Útero/patologia , Via de Sinalização Wnt/efeitos dos fármacos , beta Catenina/metabolismo
7.
Chemistry ; 25(49): 11574-11580, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31407847

RESUMO

The so-called Securinega alkaloids constitute a class of tetracyclic biologically active specialised metabolites isolated principally from subtropical plants belonging to the Phyllanthaceae family. Following a strategy based on alternative hypotheses for their biosynthesis, an easy and time-efficient divergent synthesis enabled access to twelve of those alkaloids featuring (neo)(nor)securinane skeletons. Moreover, this work permitted to reassign the absolute configurations of (+)-virosine B and (-)-episecurinol A.


Assuntos
Alcaloides/biossíntese , Alcaloides/química , Euphorbiaceae/química , Euphorbiaceae/metabolismo , Mesilatos/química , Conformação Molecular , Estereoisomerismo
8.
BMC Bioinformatics ; 20(1): 380, 2019 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-31288752

RESUMO

BACKGROUND: Alkaloids, a class of organic compounds that contain nitrogen bases, are mainly synthesized as secondary metabolites in plants and fungi, and they have a wide range of bioactivities. Although there are thousands of compounds in this class, few of their biosynthesis pathways are fully identified. In this study, we constructed a model to predict their precursors based on a novel kind of neural network called the molecular graph convolutional neural network. Molecular similarity is a crucial metric in the analysis of qualitative structure-activity relationships. However, it is sometimes difficult for current fingerprint representations to emphasize specific features for the target problems efficiently. It is advantageous to allow the model to select the appropriate features according to data-driven decisions for extracting more useful information, which influences a classification or regression problem substantially. RESULTS: In this study, we applied a neural network architecture for undirected graph representation of molecules. By encoding a molecule as an abstract graph and applying "convolution" on the graph and training the weight of the neural network framework, the neural network can optimize feature selection for the training problem. By incorporating the effects from adjacent atoms recursively, graph convolutional neural networks can extract the features of latent atoms that represent chemical features of a molecule efficiently. In order to investigate alkaloid biosynthesis, we trained the network to distinguish the precursors of 566 alkaloids, which are almost all of the alkaloids whose biosynthesis pathways are known, and showed that the model could predict starting substances with an averaged accuracy of 97.5%. CONCLUSION: We have showed that our model can predict more accurately compared to the random forest and general neural network when the variables and fingerprints are not selected, while the performance is comparable when we carefully select 507 variables from 18000 dimensions of descriptors. The prediction of pathways contributes to understanding of alkaloid synthesis mechanisms and the application of graph based neural network models to similar problems in bioinformatics would therefore be beneficial. We applied our model to evaluate the precursors of biosynthesis of 12000 alkaloids found in various organisms and found power-low-like distribution.


Assuntos
Alcaloides/classificação , Vias Biossintéticas , Redes Neurais (Computação) , Algoritmos , Alcaloides/química , Metaboloma , Modelos Teóricos
9.
Food Chem ; 298: 125067, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31260989

RESUMO

An ultra-high performance supercritical fluid chromatography-photodiode array detection-mass spectrometry (UHPSFC-MS) method for quality control of Piper longum L. has been developed and optimized. Hexane/isopropanol (70/30, v/v) was determined as the final injection solvent and methanol as the organic modifier. A design-of-experimental (DoE) approach was used to optimize column temperature, back-pressure and the gradient slope simultaneously using Trefoil CEL1 column. The back-pressure, temperature, flow rate were set at 130 bar, 32.5 °C and 1.0 mL/min, respectively. Positive electrospray ionization was used in the single ion monitoring mode. The 12 analytes were analyzed within 8 min using the optimized conditions. The linearities of the standard calibrations were satisfactory with coefficients of determination (R2) > 0.995. The recovery measured varied from 96.34% to 105.00% with relative standard deviation (RSD) ≤ 4.68%. The method was sensitive, reliable and effective, and successfully applied to simultaneous determination of 12 compounds in 28 batches of P. longum.


Assuntos
Alcaloides/química , Cromatografia com Fluido Supercrítico/métodos , Piper/química , Alcaloides/isolamento & purificação , Benzodioxóis/química , Benzodioxóis/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Cromatografia com Fluido Supercrítico/normas , Frutas/química , Frutas/metabolismo , Limite de Detecção , Espectrometria de Massas , Metanol/química , Piper/metabolismo , Piperidinas/química , Piperidinas/isolamento & purificação , Alcamidas Poli-Insaturadas/química , Alcamidas Poli-Insaturadas/isolamento & purificação , Análise de Componente Principal , Controle de Qualidade , Solventes/química , Temperatura Ambiente
10.
Phytochemistry ; 166: 112060, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31302343

RESUMO

Continued interest in bioactive alkaloids led to the isolation of four undescribed alkaloids along with 74 known ones from the aerial parts of Tabernaemontana bufalina Lour. The structures of the yet undescribed alkaloids were elucidated based on NMR, IR, UV, MS and CD spectroscopic data and X-ray crystal diffraction and, according to the plant source, named as taberhaines A-D (1-4). The known compounds comprised of 66 monoterpenoid indole, three carboline and five isoquinoline alkaloids. Among them, the known apparicine inhibited significantly the activity of xanthine oxidase, which plays an important role for gout, with an IC50 value of 0.65 µM, compared to the standard drug allopurinol (IC50 = 0.60 µM).


Assuntos
Alcaloides/química , Alcaloides/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Tabernaemontana/química , Xantina Oxidase/antagonistas & inibidores , Alcaloides/isolamento & purificação , Domínio Catalítico , Inibidores Enzimáticos/isolamento & purificação , Concentração Inibidora 50 , Modelos Moleculares , Xantina Oxidase/química
11.
Chem Biodivers ; 16(8): e1900299, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31287220

RESUMO

The biotransformation of huperzine B (hupB), one of the characteristic bioactive constituents of the medicinal plant Huperzia serrata, by a fungal endophyte of the host plant was studied. One new compound, 8α,15α-epoxyhuperzine B (1), along with two known oxygenated hupB analogs, 16-hydroxyhuperzine B (2) and carinatumin B (3), was isolated and identified. The structures of all the isolates were deduced by spectroscopic methods including NMR, MS, IR, and UV spectra. The known compounds 2 and 3 were obtained from a microbial source for the first time. To the best of our knowledge, it is the first report on the microbial transformation of hupB and would facilitate further structural modification of hupB by chemo-enzymatic method. In the LPS-induced neuro-inflammation injury assay, 8α,15α-epoxyhuperzine B (1) exhibited moderate neuroprotective activity by increasing the viability of U251 cell lines with an EC50 of 40.1 nm.


Assuntos
Alcaloides/química , Huperzia/química , Alcaloides/metabolismo , Alcaloides/farmacologia , Biotransformação , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Humanos , Huperzia/metabolismo , Lipopolissacarídeos/toxicidade , Conformação Molecular , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Plantas Medicinais/química , Plantas Medicinais/metabolismo , Substâncias Protetoras/química , Substâncias Protetoras/farmacologia
12.
Chem Pharm Bull (Tokyo) ; 67(7): 666-674, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31257322

RESUMO

Dimeric sesquiterpene thioalkaloids from the rhizomes of Nuphar pumilum exhibited immunosuppressive effects using a sheep erythrocyte plaque forming cell (PFC) assay, as well as an anti-metastasis effect, and rapid apoptosis-inducing effects in tumor cell lines. In particular, dimeric sesquiterpene thioalkaloids with a hydroxy group (6-hydroxythiobinupharidine, 6,6'-dihydroxythiobinupharidine, 6-hydroxythionuphlutine B) showed substantial effects, whereas dimeric sesquiterpene thioalkaloids lacking the hydroxy group (thiobinupharidine, thionuphlutine B, 6'-hydroxythionuphlutine B, neothiobinupharidine, thionuphlutine B ß-sulfoxide, neothiobinupharidine ß-sulfoxide) and monomeric sesquiterpene alkaloids (nupharidine, 7-epideoxynupharidine, nupharolutine) showed weak activity. In this review, we summarize our studies of the biofunctional effects of these alkaloids.


Assuntos
Alcaloides/química , Nuphar/química , Sesquiterpenos/química , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Eritrócitos/citologia , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Humanos , Imunossupressores/química , Imunossupressores/isolamento & purificação , Imunossupressores/farmacologia , Nuphar/metabolismo
13.
Planta Med ; 85(9-10): 738-744, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31185502

RESUMO

Chronic heart failure is the terminal stage of various cardiovascular diseases. Despite the availability of several classes of drugs, there is still an unmet need for effective treatment. Based on bench work during the past two decades, we have proposed that enhancement of ß 2-adrenergic receptor signaling in combination with the presently preferred ß 1-adrenergic receptor blockade would be a promising strategy. Chinese herbal medicines have been shown to be effective in the treatment of heart failure, although the mechanisms largely remain unknown. In the present study, we screened an herbal medicine compound/extract library for ß-adrenergic receptor ligands to determine the target of certain effective botanical remedies and seek a leading compound(s) for chronic heart failure treatment. Using a high-throughput screening assay, we identified higenamine, which has a long history in chronic heart failure treatment in traditional Chinese medicine, to be a potent ß-adrenergic receptor agonist. Further experiments using specific inhibitors showed that higenamine activated both ß 1-adrenergic receptor and ß 2-adrenergic receptor. Inhibition of its action by pertussis toxin (a Gi inhibitor) indicated that it is a ß 2-adrenergic receptor Gs/Gi dual agonist. Contractility experiments demonstrated a positive inotropic effect of higenamine. In conclusion, we found an herbal compound, higenamine, to be a dual agonist for ß 1/ß 2-adrenergic receptors with no preference in stimulating the Gs and Gi pathways in ß 2-adrenergic receptor signaling. Our results elucidated not only the target of higenamine to explain its pharmacological effect in treating chronic heart failure, but also the mechanisms of its cardiac toxicity.


Assuntos
Agonistas de Receptores Adrenérgicos beta 1/farmacologia , Agonistas de Receptores Adrenérgicos beta 2/farmacologia , Alcaloides/farmacologia , Medicamentos de Ervas Chinesas/química , Ensaios de Triagem em Larga Escala/métodos , Tetra-Hidroisoquinolinas/farmacologia , Alcaloides/química , Animais , Linhagem Celular , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Simulação de Acoplamento Molecular , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/fisiologia , Ratos Sprague-Dawley , Receptores Adrenérgicos beta 1/genética , Receptores Adrenérgicos beta 1/metabolismo , Receptores Adrenérgicos beta 2/genética , Receptores Adrenérgicos beta 2/metabolismo , Tetra-Hidroisoquinolinas/química
14.
AAPS PharmSciTech ; 20(6): 220, 2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-31201588

RESUMO

In this study, poly-(lactic-co-glycolic) acid (PLGA) was conjugated with aspartic acid and was characterized by nuclear magnetic resonance and Fourier transform infrared spectroscopy. Docetaxel-loaded polymeric micelles were prepared, and piperine was tagged. The neuroblastoma cytotoxicity studies revealed a substantially higher cytotoxic potential of the developed system to that of plain docetaxel, which was further corroborated by cellular uptake employing confocal laser scanning microscopy. The hemocompatible system was able to enhance the pharmacokinetic profile in terms of 6.5-fold increment in bioavailability followed by a 3.5 times increase in the retention time in comparison with the plain drug. The single-point brain bioavailability of docetaxel was amplified by 3.3-folds, signifying a better uptake and distribution to brain employing these carriers. The findings are unique as the physically adsorbed piperine was released before the DTX, increasing the propensity of curbing the CYP3A4 enzyme, which plays a vital role in the degradation of docetaxel. Meanwhile, piperine might have compromised the P-gp efflux mechanism, which can be ascribed to the enhanced retention of the drug at the target site. The elevated target site concentrations and extended residence by a biocompatible nanocarrier supplemented with co-delivery of piperine inherit immense promises to deliver this BCS class IV drug more safely and effectively.


Assuntos
Alcaloides/química , Antineoplásicos Fitogênicos/administração & dosagem , Benzodioxóis/química , Docetaxel/administração & dosagem , Micelas , Piperidinas/química , Alcamidas Poli-Insaturadas/química , Animais , Antineoplásicos Fitogênicos/farmacocinética , Disponibilidade Biológica , Encéfalo/metabolismo , Linhagem Celular Tumoral , Docetaxel/farmacocinética , Humanos , Ratos , Ratos Wistar , Espectroscopia de Infravermelho com Transformada de Fourier
15.
Mar Drugs ; 17(6)2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31151240

RESUMO

So far, the Futuna Islands located in the Central Indo-Pacific Ocean have not been inventoried for their diversity in marine sponges and associated chemical diversity. As part of the Tara Pacific expedition, the first chemical investigation of the sponge Narrabeena nigra collected around the Futuna Islands yielded 18 brominated alkaloids: seven new bromotryptamine derivatives 1-7 and one new bromotyramine derivative 8 together with 10 known metabolites of both families 9-18. Their structures were deduced from extensive analyses of nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS) data. In silico metabolite anticipation using the online tool MetWork revealed the presence of a key and minor biosynthetic intermediates. These 18 compounds showed almost no cytotoxic effect up to 10 µM on human neuroblastoma SH-SY5Y and microglia BV2 cells, and some of them exhibited an interesting neuroprotective activity by reducing oxidative damage.


Assuntos
Alcaloides/química , Alcaloides/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Poríferos/química , Alcaloides/isolamento & purificação , Alcaloides/toxicidade , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Simulação por Computador , Humanos , Internet , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Camundongos , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Fármacos Neuroprotetores/farmacologia , Oceano Pacífico , Clima Tropical
16.
Fitoterapia ; 137: 104180, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31150766

RESUMO

Effect-directed isolation of free radical scavengers from the methanol extract of the freeze-dried fruiting bodies of the cultivated basidiomycetous mushroom, black poplar (Cyclocybe cylindracea), yielded a ß-carboline alkaloid. Its structure was determined based on ESI-TOF-MS/MS, NMR and circular dichroism spectra by comparison with published data. The compound, identified as the C1-S diastereomer of brunnein B, exhibited explicit radical scavenging activity (EC50 = 119.1 ±â€¯1.2 µg/mL). The quantity of the active component was determined with HPLC-MS in the fruiting body (36.2 ±â€¯2.8 ng/g DW, dry weight) and its different tissues such as peel (94.7 ±â€¯1.9 ng/g DW), inner cap (90.5 ±â€¯1.3 ng/g DW), gills (71.5 ±â€¯0.6 ng/g DW), and stipe (162.2 ±â€¯1.7 ng/g DW). It is a ß-carboline alkaloid that was not reported previously.


Assuntos
Agaricales/química , Alcaloides/química , Carbolinas/química , Depuradores de Radicais Livres/química , Alcaloides/isolamento & purificação , Carbolinas/isolamento & purificação , Depuradores de Radicais Livres/isolamento & purificação , Hungria , Estrutura Molecular
17.
Mar Drugs ; 17(6)2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31174259

RESUMO

This review outlines the research that was carried out regarding the isolation of bioactive compounds from marine-derived bacteria and fungi by China-based research groups from 2009-2018, with 897 publications being surveyed. Endophytic organisms featured heavily, with endophytes from mangroves, marine invertebrates, and marine algae making up more than 60% of the microbial strains investigated. There was also a strong focus on fungi as a source of active compounds, with 80% of publications focusing on this area. The rapid increase in the number of publications in the field is perhaps most notable, which have increased more than sevenfold over the past decade, and suggests that China-based researchers will play a major role in marine microbial natural products drug discovery in years to come.


Assuntos
Organismos Aquáticos/química , Bactérias/química , Descoberta de Drogas , Fungos/química , Alcaloides/química , Alcaloides/isolamento & purificação , China , Peptídeos/química , Peptídeos/isolamento & purificação , Policetídeos/química , Policetídeos/isolamento & purificação , Terpenos/química , Terpenos/isolamento & purificação
18.
J Chromatogr B Analyt Technol Biomed Life Sci ; 1122-1123: 39-48, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31150952

RESUMO

Resveratrol and piperine are proven for their therapeutic benefits to treat various diseases. Due to their synergistic actions and combined drug delivery application, a rapid and specific RP-HPLC method was developed and validated as per ICH guidelines, by using an isosbestic point. The chromatographic separation was performed with Luna 5 µ 100 ŠC-18(2) HPLC column by using acetonitrile (ACN): phosphate buffer (0.01% orthophosphoric acid) (55:45) as mobile phase, at 1 mL/min of flow rate and 330 nm. The developed method was found to be linear over the concentration range of 0.25-8 µg/mL with correlation coefficient value >0.999. The developed method was accurate (percent recovery 98.06-101.74%), precise (percent relative standard deviation <2.0%), and robust. The limit of detection and limit of quantification for resveratrol were found to be 0.02 and 0.08 µg/mL, respectively and 0.04 and 0.11 µg/mL, for piperine, respectively. The developed method was also validated in human plasma as per ICH guidelines. Moreover, stress degradation studies of both phytoconstituents were studied and the relevancy of the developed method was analyzed on cubosome nanoformulation. A good separation of drug peaks was observed in the presence of the degradation products. This method could thus be used for regular in vitro and in vivo estimation of piperine and resveratrol.


Assuntos
Alcaloides/sangue , Benzodioxóis/sangue , Cromatografia Líquida de Alta Pressão/métodos , Piperidinas/sangue , Alcamidas Poli-Insaturadas/sangue , Resveratrol/sangue , Alcaloides/química , Benzodioxóis/química , Cromatografia de Fase Reversa/métodos , Estabilidade de Medicamentos , Humanos , Limite de Detecção , Modelos Lineares , Piperidinas/química , Alcamidas Poli-Insaturadas/química , Reprodutibilidade dos Testes , Resveratrol/química
19.
Mar Drugs ; 17(5)2019 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-31035362

RESUMO

Three new azaphilone alkaloids containing glutamine residues, namely N-glutarylchaetoviridins A-C (1-3), together with two related compounds (4 and 5) were isolated from the extract of Chaetomium globosum HDN151398, a fungus isolated from a deep-sea sediment sample collected in South China Sea. Their structures were elucidated on the basis of extensive 1D and 2D NMR as well as HRESIMS spectroscopic data and chemical analysis. N-glutarylchaetoviridins A-C (1-3) represent the first class of chaetoviridins characterized by embedded glutamate residues. Amino acids incubation experiments produced five azaphilone laden different amino acids residues (6-10) which indicated that this method can enhanced the structural diversity of this strain by culturing with amino acids. Cytotoxicity of the isolated compounds were evaluated against a panel of human cancer cell lines.


Assuntos
Alcaloides/farmacologia , Antineoplásicos/farmacologia , Benzopiranos/farmacologia , Chaetomium/química , Sedimentos Geológicos/microbiologia , Pigmentos Biológicos/farmacologia , Alcaloides/química , Alcaloides/isolamento & purificação , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Organismos Aquáticos/química , Benzopiranos/química , Benzopiranos/isolamento & purificação , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Glutamina/química , Humanos , Concentração Inibidora 50 , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Pigmentos Biológicos/química , Pigmentos Biológicos/isolamento & purificação
20.
Mar Drugs ; 17(5)2019 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-31035506

RESUMO

Three new diketopiperazine alkaloids, including two oxepine-containing diketopiperazines, chrysopiperazines A and B (1 and 2), and one quinazoline-containing diketopiperazine, chrysopiperazine C (5), together with three known analogues (3, 4, and 6), were isolated from the gorgonian-derived Penicillium chrysogenum fungus. The relative and absolute configurations of C-3 and C-15 in 1 and 2, C-3 and C-14 in 5 were established by NOE modified Marfey's analysis and electronic circular dichroism (ECD) calculations. Particularly, the absolute configurations of C-19 in 1 and 3, which was very challenging to be identified due to the flexible conformation in a short aliphatic chain, were successfully determined by the vibrational circular dichroism (VCD) method, supplying with a reliable and optional method to define the absolute configurations. Additionally, this is the first report on oxepine-containing diketopiperazines from the genus Penicillium.


Assuntos
Alcaloides/química , Antozoários/microbiologia , Dicetopiperazinas/química , Penicillium chrysogenum/química , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Animais , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Antifúngicos/química , Antifúngicos/isolamento & purificação , Antifúngicos/farmacologia , Bactérias/efeitos dos fármacos , Dicroísmo Circular , Dicetopiperazinas/isolamento & purificação , Dicetopiperazinas/farmacologia , Fungos/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Conformação Molecular , Estrutura Molecular , Espectroscopia de Prótons por Ressonância Magnética
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