Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 877
Filtrar
Mais filtros










Intervalo de ano de publicação
1.
Org Biomol Chem ; 17(39): 8832-8848, 2019 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-31556900

RESUMO

The reaction of indolizinones with dimethyl acetylenedicarboxylate gave direct access to 3',8a-dihydrocyclopenta[hi]indolizin-8a-ol and 1H-pyrrol-3(2H)-one in good yields. The former skeleton is a precursor to cyclazines with nitrogen on the periphery, a hitherto un-accessed 10-π system. Their formation involves initial [4 + 2] or [8 + 2] modes of cycloadditions; the retro-Diels Alder reaction of the [4 + 2] cycloadduct leads to 1H-pyrrol-3(2H)-one, whereas [8 + 2] addition followed by π-reorganization leads to the azatricyle. Analysis of substituent effects on product distribution showed that electron donating groups on the C3-aryl ring promote the formation of the azatricycle preponderantly. Treatment of one of these azatricycles (3c) with HBF4 led to the formation of the corresponding 10e-aromatic species which was detected by NMR spectroscopy. In addition, formation of the 1H-pyrrol-3(2H)-one skeleton through the normal retro-Diels Alder pathway was employed in the total synthesis of Discoipyrrole C, which is a new lead against lung cancer.


Assuntos
Alquinos/química , Compostos Heterocíclicos com 3 Anéis/química , Pirrolidinonas/química , Cristalografia por Raios X , Ciclização , Compostos Heterocíclicos com 3 Anéis/síntese química , Indolizinas/química , Modelos Moleculares , Estrutura Molecular , Pirrolidinonas/síntese química
2.
Environ Pollut ; 252(Pt B): 1593-1598, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31279977

RESUMO

Exploring traditional neonicotinoid pesticides substitutes has become one of the global scientific attentions because of their hazardous environmental impacts. Cycloxaprid (CYC) is considered to be a promising candidate alternative. But the environmental behaviors and fate of CYC in different planting system remain poorly understood. The accumulation of 14C-labeled CYC stereoisomers within different parts of Chinese cabbage (Brassica chinensis L.) was investigated, with a particular focus on the foliar absorption, translocation and stereoselectivity of CYC, during a laboratory trial. In general, the stereoisomers 14C-5R,8S-CYC and 14C-5S,8R-CYC, their metabolites, as well as the breakdown and reaction products can be transferred in both acropetal and basipetal directions. Most of the two stereoisomers absorbed by plants remained in the treated leaves, whereas a small amount was distributed to the roots. The amount of 14C in the stalks varied among the experimental time points. At 192 h after treatment (HAT), the detected radioactivity of both 14C-5R,8S-CYC and 14C-5S,8R-CYC in the leaves above the treated leaf (LATL) was higher than that in the leaves below the treated leaf (LBTL). However, the stereoisomers of CYC underwent nonstereoselective absorption and translocation in this trial. This information implies that racemic CYC and its metabolites should be a main research focus. Thus, the obtained results provide implications for a more accurate prediction about the risk assessment of CYC, which will be helpful for guiding its rational use as well as securing the ecological environment safety and human health.


Assuntos
Brassica/metabolismo , Compostos Heterocíclicos com 3 Anéis/metabolismo , Inseticidas/metabolismo , Neonicotinoides/metabolismo , Folhas de Planta/metabolismo , Piridinas/metabolismo , Transporte Biológico , Compostos Heterocíclicos com 3 Anéis/química , Inseticidas/química , Modelos Teóricos , Neonicotinoides/química , Raízes de Plantas/metabolismo , Piridinas/química , Estereoisomerismo
3.
Comput Biol Chem ; 82: 25-36, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31255972

RESUMO

The prevalence of diabetes mellitus has been incremented in the current century and the need for novel therapeutic compounds to treat this disease has been significantly increased. One of the most promising approaches is to inhibit intestinal alpha glucosidases. Based on our previous studies, four pyrimidine-fused heterocycles (PFH) were selected as they revealed satisfactory inhibitory action against mammalian α-glucosidase. The interaction of these compounds with both active domains of human maltase-glucoamylase (MGAM) and their effect on human Caco-2 cell line were investigated. The docking assessments suggested that binding properties of these ligands were almost similar to that of acarbose by establishing hydrogen bonds especially with Tyr1251 and Arg526 in both C-terminal and N-terminal MGAM, respectively. Also, these compounds indicated a stronger affinity for C-terminal of MGAM. L2 and L4 made tightly complexes with both terminals of MGAM which in turn revealed the importance of introducing pyrimidine scaffold and its hinge compartment. The results of molecular dynamics simulation analyses confirmed the docking data and showed deep penetration of L2 and L4 into the active site of MGAM. Based on cell cytotoxicity assessments, no significant cell death induction was observed. Hence, these functional MGAM inhibitors might be considered as new potential therapeutic compounds in treatment of diabetes and its complications.


Assuntos
Inibidores de Glicosídeo Hidrolases/farmacologia , Pirimidinonas/farmacologia , alfa-Glucosidases/metabolismo , Acarbose/química , Células CACO-2 , Domínio Catalítico , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/toxicidade , Compostos Heterocíclicos com 3 Anéis/química , Compostos Heterocíclicos com 3 Anéis/farmacologia , Compostos Heterocíclicos com 3 Anéis/toxicidade , Humanos , Ligações de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Ligantes , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Estrutura Molecular , Pirimidinonas/química , Pirimidinonas/toxicidade , alfa-Glucosidases/química
4.
Biotechnol Appl Biochem ; 66(5): 787-793, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31169325

RESUMO

Evidence suggests that Weichang'an (WCA) inhibited the metastasis of colorectal cancer (CRC) in vitro and downregulates oncogenic ß-catenin; more intriguingly, we also found an upregulation of ARHGAP25 in this process. This study aimed to investigate the mechanisms by which WCA regulated CRC metastasis in vitro. Here, HCT116 cells were transfected with siRNAs to interfere ARHGAP25 expression. WCA decoction, XAV939 (a specific Wnt/ß-catenin pathway inhibitor), and LiCl (an activator for Wnt/ß-catenin pathway) were used for treatment. Cell migratory and invasive capacities were determined using Transwell chamber. The activation of Wnt/ß-catenin pathway was assessed by determining the expression of MMP7, MMP9, ZEB1, and ß-catenin. The study suggests that WCA inhibited the migration and invasion of HCT116 cells and suppressed the activation of Wnt/ß-catenin pathway, as evidenced by retarding MMP7, MMP9, ZEB1, and ß-catenin. However, siRNA-ARHGAP25 resulted in the opposite. In siRNA-ARHGAP25-transfected HCT116 cells, WCA (0.4 mg/mL) induced the antimetastatic effects and the inactivation of Wnt/ß-catenin pathway was remarkably reversed with additional LiCl treatment. Our study concludes that inhibiting Wnt/ß-catenin pathway while promoting ARHGAP25 was the mechanism, whereby WCA retarded migration and invasion of CRC in vitro.


Assuntos
Movimento Celular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Proteínas Ativadoras de GTPase/metabolismo , Regulação para Cima/efeitos dos fármacos , Via de Sinalização Wnt/efeitos dos fármacos , beta Catenina/antagonistas & inibidores , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/química , Proteínas Ativadoras de GTPase/genética , Células HCT116 , Compostos Heterocíclicos com 3 Anéis/química , Compostos Heterocíclicos com 3 Anéis/farmacologia , Humanos , Relação Estrutura-Atividade , beta Catenina/metabolismo
5.
Chem Commun (Camb) ; 55(54): 7776-7779, 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31210218

RESUMO

An unusual class, compact in size, of fluorescent probes based on pyridazino-1,3a,6a-triazapentalene scaffolds exhibits promising fluorescent properties (quantum yield values up to 73%, large Stokes shifts, emission wavelengths located in the green-yellow range, excellent solubility) with good photostability suitable for optical imaging applications.


Assuntos
Corantes Fluorescentes/química , Compostos Heterocíclicos com 3 Anéis/química , Fluorescência , Corantes Fluorescentes/síntese química , Células HeLa , Compostos Heterocíclicos com 3 Anéis/síntese química , Humanos , Microscopia de Fluorescência/métodos , Imagem Óptica/métodos , Fotodegradação
6.
Colloids Surf B Biointerfaces ; 178: 404-411, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30903979

RESUMO

Previous research has shown that ectoines fluidize lipid monolayers by increasing the liquid expanded region in DPPC monolayers and also decreasing the line tension responsible for the phase morphology. Here, we explored possible effects of the compatible osmolytes ectoine, hydroxyectoine and ß-hydroxybutyrate on lipid bilayer membranes, including effects of temperature and pressure. The effect of the protective osmolytes on the phase transition of DPPC bilayers was investigated by fluorescence spectroscopy, differential scanning calorimetry and pressure perturbation calorimetry. A slight change of the phase behavior was observed, which resulted in a stabilization of the gel phase, which may be caused by an alteration of the hydration properties at the lipid interface and H-bond and electrostatic interactions in the headgroup region. We then explored the cosolvents' effects on giant unilamellar vesicles (GUVs) formed by lipid mixtures exhibiting phase separation into liquid-ordered (lo) and liquid-disordered (ld) domains using BODIPY-PC and the DiI18 dye as labels. The presence of both, ectoine and hydroxyectoine showed significant effects on the lateral organization increasing the fluid domains. Moreover, we observed a considerable increase in the adhesion behavior of small vesicles onto GUV surfaces. Diffusion studies by fluorescence recovery after photobleaching experiments on POPC giant vesicles quantitatively showed a hydroxyectoine-induced increase of the diffusion coefficient values, clearly demonstrating an increase in the lateral mobility of lipid within the bilayer membrane. This study provides clear evidence for the fluidizing effect of the compatible solutes on bilayer lipid membranes. A marked effect, however, was only detected if phase separated domains exist.


Assuntos
Ácido 3-Hidroxibutírico/química , Diamino Aminoácidos/química , Bicamadas Lipídicas/química , Fosfolipídeos/química , Compostos de Boro/química , Compostos Heterocíclicos com 3 Anéis/química , Transição de Fase , Fosfatidilcolinas/química , Pressão , Temperatura Ambiente , Lipossomas Unilamelares/química
7.
Carbohydr Res ; 474: 34-42, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30711766

RESUMO

Legionaminic acid and 4-epi-legionaminic acid are 5,7-diacetamido nonulosonic acids and are assumed to play a crucial role in the virulence of Legionella pneumophila, the causative agent of Legionnaires' disease. Moreover, they are ideal target motifs for the development of vaccines and pathogen detection. Herein, we present a versatile de novo synthesis of legionaminic acid and 4-epi-legionaminic acid. Starting from simple d-serine, the C9-backbone is built up by two CC-bond formation reactions. First, the protected d-serine motif is elongated utilizing a highly stereoselective nitroaldol reaction to give a C6-precursor of desired d-rhamno configuration. Second, an indium-mediated allylation is employed to further elongate the carbon backbone and introduce a masked α-keto acid function.


Assuntos
Técnicas de Química Sintética , Compostos Heterocíclicos com 3 Anéis/química , Nitrocompostos/química , Serina/química , Ácidos Siálicos/síntese química , Açúcares Ácidos/química , Catálise , Humanos , Índio/química , Cinética , Legionella pneumophila/metabolismo , Estrutura Molecular , Estereoisomerismo
8.
Mar Drugs ; 17(1)2019 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-30634617

RESUMO

The purpose of this study was to investigate the antiobesity effect and the mechanism of action of diphlorethohydroxycarmalol (DPHC) isolated from Ishige okamurae in 3T3-L1 cells. The antiobesity effects were examined by evaluating intracellular fat accumulation in Oil Red O-stained adipocytes. Based on the results, DPHC dose-dependently inhibited the lipid accumulation in 3T3-L1 adipocytes. DPHC significantly inhibited adipocyte-specific proteins such as SREBP-1c, PPARγ, C/EBP α, and adiponectin, as well as adipogenic enzymes, including perilipin, FAS, FABP4, and leptin in adipocytes. These results indicated that DPHC primarily acts by regulating adipogenic-specific proteins through inhibiting fat accumulation and fatty acid synthesis in adipocytes. DPHC treatment significantly increased both AMPK and ACC phosphorylation in adipocytes. These results indicate that DPHC inhibits the fat accumulation by activating AMPK and ACC in 3T3-L1 cells. Taken together, these results suggest that DPHC can be used as a potential therapeutic agent against obesity.


Assuntos
Adenilato Quinase/metabolismo , Adipócitos/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Compostos Heterocíclicos com 3 Anéis/farmacologia , Células 3T3-L1 , Adenilato Quinase/genética , Animais , Sobrevivência Celular , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Compostos Heterocíclicos com 3 Anéis/química , Camundongos , Estrutura Molecular , Alga Marinha/química
9.
Nat Prod Res ; 33(20): 3011-3015, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30445873

RESUMO

With the help of chemical shifts computed with density functional theory (DFT), it is demonstrated that the reported experimental 13C NMR data of acremolin C are incompatible with the claimed structure of an N2,3-ethenoguanine with an isopropyl group at C-1'. An alternative structure, which is in agreement with both experimental and computed data, presents an isopropyl group at the C-2' position of an N2,3-ethenoguanine and leads to the conclusion that acremolin C is identical with acremolin B.


Assuntos
Alcaloides/química , Compostos Heterocíclicos com 3 Anéis/química , Estrutura Molecular , Teoria da Densidade Funcional , Espectroscopia de Ressonância Magnética , Teoria Quântica
10.
Talanta ; 192: 233-240, 2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30348383

RESUMO

Probe encapsulated by biologically localized embedding (PEBBLE) has emerged as a new type of sensing technique for complex systems. Generalized ratiometric PEBBLE nanosensors prepared by encapsulating an intensity-based probe and an inert reference dye inside the pores of stable matrix possess advantages of easy synthesis, immunity to interference, lower toxicity, and robustness to variations in probe loading. However, the selection of appropriate reference dyes used in generalized ratiometric PEBBLE nanosensors is a rather difficult task since they should satisfy some stringent requirements. In this contribution, the feasibility of using carbon dots (C-dots) as generic inert references in synthesizing PEBBLE nanosensors was first investigated in detail. And a dual-wavelength monitoring strategy and the quantitative fluorescence model for generalized ratiometric probes (QFMGRP) were adopted to solve the problems brought by the use of carbon dots as inert references. C-dots doped PEBBLE nanosensors (C-PEBBLE nanosensors) for the quantification of NO2- and free Ca2+ were synthesized by encapsulating C-dots and intensity based fluorescence probes (i.e., acriflavine for NO2-, and Rhod-2 for Ca2+, respectively) inside the pores of stable matrix. Experimental results showed that the combination of C-PEBBLEs, the QFMGRP model and the dual-wavelength monitoring strategy achieved accurate quantification of NO2- and the free Ca2+ in real-world samples. Their quantitative results were in good consistence with those determined by HPLC and atomic absorption spectrophotometer, respectively. The strategies proposed in this contribution have generic applicability in the synthesis of PEBBLE nanosensors and their quantitative applications.


Assuntos
Carbono/química , Corantes Fluorescentes/química , Pontos Quânticos/química , Acriflavina/química , Resinas Acrílicas/química , Cálcio/análise , Fluorescência , Compostos Heterocíclicos com 3 Anéis/química , Limite de Detecção , Nitritos/análise , Tamanho da Partícula , Polimerização , Porosidade , Espectrometria de Fluorescência/métodos
11.
Artigo em Inglês | MEDLINE | ID: mdl-30572204

RESUMO

Dolutegravir, elvitegravir, raltegravir, nevirapine and etravirine are antiretroviral drugs used as part of combined antiretroviral treatment for HIV-infection. For quantification of these drugs in human K2EDTA plasma samples an ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) bioanalytical method was developed and validated. Stable isotope labeled internal standards were used for each analyte. Simple protein precipitation with methanol was implemented to prepare plasma samples of at least 50 µL. The method was validated for dolutegravir, elvitegravir, raltegravir, nevirapine and etravirine over the ranges 9.7-9700, 52-10,470, 9.7-9730, 73-14,680 and 15-3010 ng/mL, respectively. Within-run and between-run accuracy and precision were within ±15% of the nominal concentration for quality controls at high, medium and low concentrations, and within ±20% at the lower limit of quantification for all analytes. Recovery was ≥76% and reproducible. Long-term stability of patient plasma samples was demonstrated for at least 12 months at -40 °C (4 months for etravirine). Currently, this robust method with a run time of 10 min is used in clinical research and for therapeutic drug monitoring of these frequently used antiretroviral drugs.


Assuntos
Antirretrovirais/sangue , Cromatografia Líquida de Alta Pressão/métodos , Compostos Heterocíclicos com 1 Anel/sangue , Compostos Heterocíclicos com 3 Anéis/sangue , Quinolonas/sangue , Antirretrovirais/química , Antirretrovirais/farmacocinética , Estabilidade de Medicamentos , Compostos Heterocíclicos com 1 Anel/química , Compostos Heterocíclicos com 1 Anel/farmacocinética , Compostos Heterocíclicos com 3 Anéis/química , Compostos Heterocíclicos com 3 Anéis/farmacocinética , Humanos , Limite de Detecção , Modelos Lineares , Quinolonas/química , Quinolonas/farmacocinética , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem/métodos
12.
Biofouling ; 34(8): 950-961, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30539667

RESUMO

A range of natural products from marine invertebrates, bacteria and fungi have been assessed as leads for nature-inspired antifouling (AF) biocides, but little attention has been paid to microalgal-derived compounds. This study assessed the AF activity of the spirocyclic imine portimine (1), which is produced by the benthic mat-forming dinoflagellate Vulcanodinium rugosum. Portimine displayed potent AF activity in a panel of four macrofouling bioassays (EC50 0.06-62.5 ng ml-1), and this activity was distinct from that of the related compounds gymnodimine-A (2), 13-desmethyl spirolide C (3), and pinnatoxin-F (4). The proposed mechanism of action for portimine is induction of apoptosis, based on the observation that portimine inhibited macrofouling organisms at developmental stages known to involve apoptotic processes. Semisynthetic modification of select portions of the portimine molecule was subsequently undertaken. Observed changes in bioactivity of the resulting semisynthetic analogues of portimine were consistent with portimine's unprecedented 5-membered imine ring structure playing a central role in its AF activity.


Assuntos
Alcaloides/farmacologia , Incrustação Biológica/prevenção & controle , Compostos Heterocíclicos com 3 Anéis/farmacologia , Hidrocarbonetos Cíclicos/farmacologia , Iminas/farmacologia , Microalgas/química , Compostos de Espiro/farmacologia , Alcaloides/síntese química , Alcaloides/química , Organismos Aquáticos/efeitos dos fármacos , Compostos Heterocíclicos com 3 Anéis/síntese química , Compostos Heterocíclicos com 3 Anéis/química , Hidrocarbonetos Cíclicos/síntese química , Hidrocarbonetos Cíclicos/química , Iminas/síntese química , Iminas/química , Estrutura Molecular , Compostos de Espiro/síntese química , Compostos de Espiro/química , Relação Estrutura-Atividade
13.
Nature ; 563(7733): 652-656, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30464344

RESUMO

The strigolactones, a class of plant hormones, regulate many aspects of plant physiology. In the inhibition of shoot branching, the α/ß hydrolase D14-which metabolizes strigolactone-interacts with the F-box protein D3 to ubiquitinate and degrade the transcription repressor D53. Despite the fact that multiple modes of interaction between D14 and strigolactone have recently been determined, how the hydrolase functions with D3 to mediate hormone-dependent D53 ubiquitination remains unknown. Here we show that D3 has a C-terminal α-helix that can switch between two conformational states. The engaged form of this α-helix facilitates the binding of D3 and D14 with a hydrolysed strigolactone intermediate, whereas the dislodged form can recognize unmodified D14 in an open conformation and inhibits its enzymatic activity. The D3 C-terminal α-helix enables D14 to recruit D53 in a strigolactone-dependent manner, which in turn activates the hydrolase. By revealing the structural plasticity of the SCFD3-D14 ubiquitin ligase, our results suggest a mechanism by which the E3 coordinates strigolactone signalling and metabolism.


Assuntos
Compostos Heterocíclicos com 3 Anéis/metabolismo , Lactonas/metabolismo , Oryza/enzimologia , Oryza/metabolismo , Reguladores de Crescimento de Planta/metabolismo , Proteínas Ligases SKP Culina F-Box/química , Proteínas Ligases SKP Culina F-Box/metabolismo , Transdução de Sinais , Compostos Heterocíclicos com 3 Anéis/química , Lactonas/química , Modelos Moleculares , Complexos Multienzimáticos/antagonistas & inibidores , Complexos Multienzimáticos/química , Complexos Multienzimáticos/metabolismo , Reguladores de Crescimento de Planta/química , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Ligação Proteica , Estrutura Secundária de Proteína , Proteínas Ligases SKP Culina F-Box/antagonistas & inibidores , Relação Estrutura-Atividade , Ubiquitina , Ubiquitinação
14.
Org Lett ; 20(22): 7216-7219, 2018 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-30394749

RESUMO

A nickel-catalyzed oxidative decarboxylative annulation reaction of simple benzamides and (hetero)aromatic carboxylates has been developed. This reaction provides access to a large array of phenanthridinones and their heterocyclic analogues, highlighting the utility and versatility of oxidative decarboxylative coupling strategies for C-C bond formation.


Assuntos
Benzamidas/química , Ácidos Carboxílicos/química , Compostos Heterocíclicos com 3 Anéis/síntese química , Fenantrenos/síntese química , Catálise , Compostos Heterocíclicos com 3 Anéis/química , Estrutura Molecular , Níquel/química , Oxirredução , Fenantrenos/química
15.
Chem Commun (Camb) ; 54(100): 14089-14092, 2018 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-30480281

RESUMO

Sulfonamide derivatives have been used in pharmaceutics for decades. Here we report a new approach to release sulfonamides efficiently using a bioorthogonal reaction of sulfonyl sydnonimines and dibenzoazacyclooctyne (DIBAC). The second-order rate constant of the cycloaddition reaction can be up to 0.62 M-1 s-1, and the reactants are highly stable under physiological conditions. Most significantly, we also discovered the mutual orthogonality between the sydnonimine-DIBAC and benzonorbornadiene-tetrazine cycloaddition pairs, which can be used for selective and simultaneous liberation of sulfonamide and primary amine drugs.


Assuntos
Compostos Azabicíclicos/química , Celecoxib/síntese química , Doxorrubicina/síntese química , Compostos Heterocíclicos com 3 Anéis/química , Pró-Fármacos/química , Sidnonas/química , Compostos Azabicíclicos/síntese química , Celecoxib/química , Química Click , Reação de Cicloadição , Ciclo-Oxigenase 2/química , Inibidores de Ciclo-Oxigenase/síntese química , Inibidores de Ciclo-Oxigenase/química , Ensaios Enzimáticos , Compostos Heterocíclicos com 3 Anéis/síntese química , Humanos , Modelos Químicos , Pró-Fármacos/síntese química , Teoria Quântica , Sidnonas/síntese química
16.
Mar Drugs ; 16(11)2018 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-30441860

RESUMO

Cyclic imine toxins are neurotoxic, macrocyclic compounds produced by marine dinoflagellates. Mass spectrometric screenings of extracts from natural plankton assemblages revealed a high chemical diversity among this toxin class, yet only few toxins are structurally known. Here we report the structural characterization of four novel cyclic-imine toxins (two gymnodimines (GYMs) and two spirolides (SPXs)) from cultures of Alexandrium ostenfeldii. A GYM with m/z 510 (1) was identified as 16-desmethylGYM D. A GYM with m/z 526 was identified as the hydroxylated degradation product of (1) with an exocyclic methylene at C-17 and an allylic hydroxyl group at C-18. This compound was named GYM E (2). We further identified a SPX with m/z 694 as 20-hydroxy-13,19-didesmethylSPX C (10) and a SPX with m/z 696 as 20-hydroxy-13,19-didesmethylSPX D (11). This is the first report of GYMs without a methyl group at ring D and SPXs with hydroxyl groups at position C-20. These compounds can be conceived as derivatives of the same nascent polyketide chain, supporting the hypothesis that GYMs and SPXs are produced through common biosynthetic genes. Both novel GYMs 1 and 2 were detected in significant amounts in extracts from natural plankton assemblages (1: 447 pg; 2: 1250 pg; 11: 40 pg per mL filtered seawater respectively).


Assuntos
Dinoflagelados/química , Compostos Heterocíclicos com 3 Anéis/química , Hidrocarbonetos Cíclicos/química , Iminas/química , Toxinas Marinhas/química , Fitoplâncton/química , Compostos de Espiro/química , Compostos Heterocíclicos com 3 Anéis/isolamento & purificação , Hidrocarbonetos Cíclicos/isolamento & purificação , Iminas/isolamento & purificação , Toxinas Marinhas/isolamento & purificação , Estrutura Molecular , Compostos de Espiro/isolamento & purificação
17.
Chem Commun (Camb) ; 54(83): 11749-11752, 2018 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-30276367

RESUMO

In the first example of site-directed spin-labeling of unmodified RNA, a pyrrolidine-nitroxide derivative of tetramethylrosamine (TMR) was shown to bind with high affinity to the malachite green (MG) aptamer, as determined by continuous-wave (CW) electron paramagnetic resonance (EPR), pulsed electron-electron double resonance (PELDOR) and fluorescence spectroscopies.


Assuntos
Aptâmeros de Nucleotídeos/química , RNA/química , Marcadores de Spin , Sítios de Ligação , Espectroscopia de Ressonância de Spin Eletrônica , Compostos Heterocíclicos com 3 Anéis/química , Modelos Moleculares , Pirrolidinas/química , Rodaminas , Corantes de Rosanilina/análise , Espectrometria de Fluorescência , Marcadores de Spin/síntese química
18.
Anal Bioanal Chem ; 410(29): 7773-7781, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30280227

RESUMO

Measurement of drug concentrations in hair provides a non-invasive approach to assess drug adherence. Here, we report on the development and validation of a method for the quantification of the antiretroviral dolutegravir (DTG) extracted from human hair. DTG is extracted from hair samples by sonication and incubation in 50:50 methanol:acetonitrile with 2% formic acid overnight at 40 °C. Following extraction, samples are analyzed by reverse-phase chromatography on a Waters Atlantis T3 (50 × 2.1 mm, 3-µm particle size) column with subsequent detection by electrospray ionization in positive ion mode on an AB Sciex API-5000 triple quadrupole mass spectrometer. The stable, isotopically labeled 13C,d5-DTG is used as an internal standard in the assay. The calibration range is 5-10,000 pg DTG/mL of extraction solvent with the ability to extract between 1 and 10 mg of hair/mL of extraction solvent. The assay was linear, accurate (inter-assay %bias within ± 6.5%), and precise (inter-assay %CV ≤ 10.3%). The assay was successfully used to analyze clinical samples from subjects on DTG regimens. Analysis of clinical samples suggested the potential presence of a degradation product, which was subsequently confirmed to occur with exposure to sunlight. The degradation of DTG could complicate absolute interpretation of clinical results, but the presence of this degradation product is easily evaluated with this assay to aid in data interpretation.


Assuntos
Cabelo/química , Compostos Heterocíclicos com 3 Anéis/química , Cromatografia Líquida/métodos , Humanos , Padrões de Referência , Espectrometria de Massas em Tandem/métodos
19.
Org Lett ; 20(18): 5922-5926, 2018 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-30199265

RESUMO

Natural products from environmental microbiomes provide exquisite templates for elucidating biological activity in the search for new drugs. A recently discovered marine Brevibacillus sp. metabolite, ulbactin F, was found to inhibit tumor cell migration and invasion at IC50 < 3 µM. Herein, we disclose the first total synthesis of ulbactin F and epi-ulbactin F, which was modeled after the biosynthetic pathway. The scaffold bears structural similarity to siderophores of human pathogens but contains a novel tricyclic ring system derived from cysteine. We have found that ulbactin F forms low-affinity metal complexes, with a preference for Fe3+ and Cu2+, which may hint both at its environmental role and its antimetastatic mechanism of action.


Assuntos
Antibacterianos/síntese química , Produtos Biológicos/síntese química , Compostos Heterocíclicos com 3 Anéis/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Brevibacillus/química , Compostos Heterocíclicos com 3 Anéis/química , Compostos Heterocíclicos com 3 Anéis/farmacologia , Testes de Sensibilidade Microbiana , Estrutura Molecular , Pseudomonas aeruginosa/efeitos dos fármacos , Estereoisomerismo , Termodinâmica
20.
Chem Commun (Camb) ; 54(84): 11865-11868, 2018 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-30204158

RESUMO

Detection of biofilm bacteria would be an ideal method for the physicians to diagnose chronic bacterial infections directly, but there are few imaging probes available so far. Here, we report the development of a novel biofilm detecting fluorescent probe, CDy14, through an unbiased screening of a fluorescence library and elucidated its binding partner Psl, an exopolysaccharide of the biofilm.


Assuntos
Biofilmes , Compostos de Boro/química , Corantes Fluorescentes/metabolismo , Compostos Heterocíclicos com 3 Anéis/química , Polissacarídeos Bacterianos/metabolismo , Corantes Fluorescentes/química , Microscopia de Fluorescência , Polissacarídeos Bacterianos/química , Pseudomonas aeruginosa/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA