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1.
Biomed Chromatogr ; 34(1): e4712, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31633799

RESUMO

Coffee and tea are the most widely consumed beverages worldwide. However, the consumer may be unaware of the exact amount of methyl xanthine (MX, i.e. caffeine [C], theobromine [TB] and theophylline [TH]) consumed, as most of the products do not list the proper amounts. This may lead to serious risks including cardiovascular, kidney and stimulant effects. The aim of the study was to determine the MX amount in ready-to-use beverages (coffee and tea) collected from various outlets in the city of Al-Khobar, Saudi Arabia. Forty different samples of espresso, black coffee and red tea were collected. A fast, reliable and efficient UHPLC-DAD method was developed and validated for MX determination. Total lipids were extracted and fractionated in order to determine glycolipids, phospholipids and neutral lipids. The r2 value for the method was 0.980-0.988 in a linearity range of 0.5-200 ppm. The range for MX (C [0.02-2.39 mg/ml], TB [0.00-0.10 mg/ml] and TH [0.00-0.004 mg/ml]) and total lipids was 1-5 g. The amount of glycolipids (3.1 g) was higher among the lipid fractions followed by phospholipids (1.8 g) and neutral lipids (0.25 g). In general, espresso beverages (20-30 ml) contained high amounts of MX whereas black coffee beverages contained high amount of lipids. Most of the beverages expressed C, TB, TH, lipids or their fractions; however, the product with high amounts of MX and lipids at the same time was espresso (brands Chemistry and Wogard). Although the MX and lipid levels in these beverages well below the allowed limits, care must still be taken, especially when using the beverages with high serving volumes (200-250 ml) or coffee prepared via the filter method i.e. black coffee, using a high temperature for a longer time.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Café/química , Chá/química , Xantinas , Culinária , Temperatura Alta , Lipídeos/análise , Reprodutibilidade dos Testes , Arábia Saudita , Xantinas/análise , Xantinas/química , Xantinas/isolamento & purificação
2.
Phys Chem Chem Phys ; 21(48): 26430-26437, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31774088

RESUMO

We explore the influence of the relative position of the methyl substituent on the photophysics of theophylline and theobromine, two molecules that are structurally related to the DNA bases. Using a combination of spectroscopic techniques and quantum mechanical calculations, we show that moving the methyl group from N1 in theophylline to N7 in theobromine causes significant differences in their excited state properties, i.e., it produces pyramidalization of N7 in the excited state of the latter. Paradoxically, this modification seems to have little effect on the structural properties of the cation and the ionization process. It is suggested that similar effects may exist in the excited state properties of DNA bases.


Assuntos
Teobromina/química , Teofilina/química , Xantinas/química , Espectroscopia Fotoeletrônica , Espectrofotometria
3.
J Agric Food Chem ; 67(34): 9501-9509, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31334642

RESUMO

Composition of bioactive compounds in cocoa beans is critical to the sensory and nutritional quality of cocoa based products. Twenty-six cocoa bean genotypes were freshly collected from the same plantation location in Indonesia. The bioactive compounds in these raw cocoa genotypes were identified and quantified. The results showed a great diversity in the composition of bioactive compounds among the 26 cocoa samples. The concentrations of methylxanthines, epicatechin, proanthocyanidin (PA) B-type oligomers, clovamide, and anthocyanins were important variables that differentiated these genotypes. MCC 01, SUL 3, ICCRI 03, and ICS 60 genotypes had the highest contents of flavan-3-ols including PAs and have the potential to be developed for "healthy" product formulations. Some genotypes such as DR 1, DR 2, DR 38, ICS 13, KPC 1, KW 617, RCC 71, and TSH 858 could be favored by industries due to the potential to be made into end-products with brighter appearance.


Assuntos
Cacau/química , Cacau/genética , Extratos Vegetais/química , Cacau/classificação , Catequina/química , Flavonoides , Genótipo , Indonésia , Proantocianidinas/química , Sementes/química , Sementes/genética , Xantinas/química
4.
J Pharmacol Exp Ther ; 370(3): 350-359, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31201216

RESUMO

Glucose-stimulated insulin secretion from pancreatic ß-cells is controlled by ATP-regulated potassium (KATP) channels composed of Kir6.2 and sulfonylurea receptor 1 (SUR1) subunits. The KATP channel-opener diazoxide is FDA-approved for treating hyperinsulinism and hypoglycemia but suffers from off-target effects on vascular KATP channels and other ion channels. The development of more specific openers would provide critically needed tool compounds for probing the therapeutic potential of Kir6.2/SUR1 activation. Here, we characterize a novel scaffold activator of Kir6.2/SUR1 that our group recently discovered in a high-throughput screen. Optimization efforts with medicinal chemistry identified key structural elements that are essential for VU0071063-dependent opening of Kir6.2/SUR1. VU0071063 has no effects on heterologously expressed Kir6.1/SUR2B channels or ductus arteriole tone, indicating it does not open vascular KATP channels. VU0071063 induces hyperpolarization of ß-cell membrane potential and inhibits insulin secretion more potently than diazoxide. VU0071063 exhibits metabolic and pharmacokinetic properties that are favorable for an in vivo probe and is brain penetrant. Administration of VU0071063 inhibits glucose-stimulated insulin secretion and glucose-lowering in mice. Taken together, these studies indicate that VU0071063 is a more potent and specific opener of Kir6.2/SUR1 than diazoxide and should be useful as an in vitro and in vivo tool compound for investigating the therapeutic potential of Kir6.2/SUR1 expressed in the pancreas and brain.


Assuntos
Ativação do Canal Iônico/efeitos dos fármacos , Canais de Potássio Corretores do Fluxo de Internalização/metabolismo , Receptores Sulfonilureia/metabolismo , Xantinas/farmacologia , Xantinas/farmacocinética , Animais , Canal Arterial/efeitos dos fármacos , Canal Arterial/fisiologia , Glucose/farmacologia , Células HEK293 , Humanos , Secreção de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/citologia , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Camundongos , Relação Estrutura-Atividade , Vasodilatação/efeitos dos fármacos , Xantinas/química
5.
Molecules ; 24(12)2019 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-31212849

RESUMO

In earlier studies, we generated concentration-response (E/c) curves with CPA (N6-cyclopentyladenosine; a selective A1 adenosine receptor agonist) or adenosine, in the presence or absence of S-(2-hydroxy-5-nitrobenzyl)-6-thioinosine (NBTI, a selective nucleoside transport inhibitor), and with or without a pretreatment with 8-cyclopentyl-N3-[3-(4-(fluorosulfonyl)-benzoyloxy)propyl]-N1-propylxanthine (FSCPX, a chemical known as a selective, irreversible A1 adenosine receptor antagonist), in isolated, paced guinea pig left atria. Meanwhile, we observed a paradoxical phenomenon, i.e. the co-treatment with FSCPX and NBTI appeared to enhance the direct negative inotropic response to adenosine. In the present in silico study, we aimed to reproduce eight of these E/c curves. Four models (and two additional variants of the last model) were constructed, each one representing a set of assumptions, in order to find the model exhibiting the best fit to the ex vivo data, and to gain insight into the paradoxical phenomenon in question. We have obtained in silico evidence for an interference between effects of FSCPX and NBTI upon our ex vivo experimental setting. Regarding the mechanism of this interference, in silico evidence has been gained for the assumption that FSCPX inhibits the effect of NBTI on the level of endogenous (but not exogenous) adenosine. As an explanation, it may be hypothesized that FSCPX inhibits an enzyme participating in the interstitial adenosine formation. In addition, our results suggest that NBTI does not stop the inward adenosine flux in the guinea pig atrium completely.


Assuntos
Antagonistas do Receptor A1 de Adenosina/química , Proteínas de Transporte de Nucleobases/química , Receptor A1 de Adenosina/química , Xantinas/química , Adenosina/química , Adenosina/farmacologia , Antagonistas do Receptor A1 de Adenosina/farmacologia , Animais , Relação Dose-Resposta a Droga , Cobaias , Proteínas de Transporte de Nucleobases/antagonistas & inibidores , Xantinas/farmacologia
6.
Eur J Med Chem ; 176: 117-128, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31108261

RESUMO

A series of novel xanthine/NO donor hybrids containing 1,3,8-trisubstituted or 1,8-disubstituted xanthine derivatives were designed and synthesized. The synthesized compounds were tested in a cell viability assay using human mammary gland epithelial cell line (MCF-10A) where all the compounds exhibited no cytotoxic effects and more than 90% cell viability at a concentration of 50 µM. The oxime containing compounds 7a-b and 17-24 were more active as antiproliferative agents than their non-oxime congeners 6a-b and 9-16. Hydroxyimino-phenethyl scaffold compounds 17-24 were more active than the hydroxyimino-ethyl phenyl acetamide 7a-b derivatives. Compounds 18-20 and 22-24 exhibited inhibition of EGFR with IC50 ranging from 0.32 to 2.88 µM. Compounds 18-20 and 22-24 increased the level of active caspase 3 by 4-8 folds, compared to the control cells in Panc-1 cell lines compared to doxorubicin as a reference drug. Compounds 18, 22 and 23 were the most caspase-3 inducers. Compounds 22 and 23 increased the levels of caspase-8 and 9 indicating activation of both intrinsic and extrinsic pathways and showed potent induction of Bax, down-regulation of Bcl-2 protein levels and over-expression of cytochrome c levels in Panc-1 human pancreas cancer cells. Compound 23 exhibited mainly cell cycle arrest at the Pre-G1 and G2/M phases in the cell cycle analysis of Panc-1 cell line. The drug likeness profiles of compounds 18-20 and 22-24 were predicted to have good to excellent drug likeness profiles specially compounds 18-20 and 23. Finally molecular docking study was performed at the EGFR active site to suggest thier possible binding mode. The hydroxyimino-phenethyl scaffold compounds 17-24 represent an interesting starting point to optimize their pharmacokinetics and pharmacodynamics profiles.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Oximas/farmacologia , Xantinas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/toxicidade , Caspase 3/metabolismo , Caspase 8/metabolismo , Caspase 9/metabolismo , Domínio Catalítico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Citocromos c/metabolismo , Ensaios de Seleção de Medicamentos Antitumorais , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/química , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Oximas/síntese química , Oximas/química , Oximas/toxicidade , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Relação Estrutura-Atividade , Xantinas/síntese química , Xantinas/química , Xantinas/toxicidade , Proteína X Associada a bcl-2/metabolismo
7.
Biomolecules ; 9(5)2019 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-31137572

RESUMO

This paper presents an analysis of the molecular mechanisms involved in the formation of inclusion complexes together with some structural interpretation of drug-carrier molecule interactions in aqueous multicomponent systems comprising methylxanthines and cyclodextrins. The determination of apparent partial molar volumes (Φv) from experimental density measurements, both for binary and ternary aqueous solutions of cyclodextrins and methylxanthines, was performed at low concentration range to be consistent with their therapeutic uses in the drug-releasing field. The estimation of the equilibrium constant for inclusion complexes of 1:1 stoichiometry was done through the mathematical modelling of this apparent molar property. The examination of the volume changes offered information about the driving forces for the insertion of the xanthine into the cyclodextrin molecule. The analysis on the volumes of transfer, Δ, Φv,c and the viscosity B-coefficients of transfer, ΔB, for the xanthine from water to the different aqueous solutions of cyclodextrin allowed evaluating the possible interactions between aqueous solutes and/or solute-solvent interactions occurring in the solution. Mutual diffusion coefficients for binary, and ternary mixtures composed by xanthine, cyclodextrin, and water were measured with the Taylor dispersion technique. The behavior diffusion of these multicomponent systems and the coupled flows occurring in the solution were analyzed in order to understand the probable interactions between cyclodextrin-xanthine by estimating their association constants and leading to clearer insight of these systems structure. The measurements were performed at the standard (298.15 ± 0.01) K and physiological (310.15 ± 0.01) K temperatures.


Assuntos
Ciclodextrinas/química , Portadores de Fármacos/química , Xantinas/química , Difusão , Termodinâmica , Viscosidade
8.
FEBS Open Bio ; 9(4): 717-727, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30984545

RESUMO

In eukaryotic cells, cytoplasmic mRNA is characterised by a 3' poly(A) tail. The shortening and removal of poly(A) tails (deadenylation) by the Ccr4-Not nuclease complex leads to reduced translational efficiency and RNA degradation. Using recombinant human Caf1 (CNOT7) enzyme as a screening tool, we recently described the discovery and synthesis of a series of substituted 1-hydroxy-3,7-dihydro-1H-purine-2,6-diones (1-hydroxy-xanthines) as inhibitors of the Caf1 catalytic subunit of the Ccr4-Not complex. Here, we used a chemiluminescence-based AMP detection assay to show that active 1-hydroxy-xanthines inhibit both isolated Caf1 enzyme and human Caf1-containing complexes that also contain the second nuclease subunit Ccr4 (CNOT6L) to a similar extent, indicating that the active site of the Caf1 nuclease subunit does not undergo substantial conformational change when bound to other Ccr4-Not subunits. Using differential scanning fluorimetry, we also show that binding of active 1-hydroxy-xanthines requires the presence of Mg2+ ions, which are present in the active site of Caf1.


Assuntos
Magnésio/química , Ribonucleases/metabolismo , Fatores de Transcrição/metabolismo , Xantinas/química , Humanos , Íons/química , Ribonucleases/química , Fatores de Transcrição/química
9.
Crit Rev Food Sci Nutr ; 59(16): 2597-2625, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29624433

RESUMO

Methylated xanthines (methylxanthines) are available from a significant number of different botanical species. They are ordinarily included in daily diet, in many extremely common beverages and foods. Caffeine, theophylline and theobromine are the main methylxanthines available from natural sources. The supposedly relatively low toxicity of methylxanthines, combined with the many beneficial effects that have been attributed to these compounds through time, generated a justified attention and a very prolific ground for dedicated scientific reports. Methylxanthines have been widely used as therapeutical tools, in an intriguing range of medicinal scopes. In fact, methylxanthines have been/were medically used as Central Nervous System stimulants, bronchodilators, coronary dilators, diuretics and anti-cancer adjuvant treatments. Other than these applications, methylxanthines have also been hinted to hold other beneficial health effects, namely regarding neurodegenerative diseases, cardioprotection, diabetes and fertility. However, it seems now consensual that toxicity concerns related to methylxanthine consumption and/or therapeutic use should not be dismissed. Taking all the knowledge and expectations on the potential of methylxanthines into account, we propose a systematic look at the past and future of methylxanthine pharmacologic applications, discussing all the promise and anticipating possible constraints. Anyways, methylxanthines will still substantiate considerable meaningful research and discussion for years to come.


Assuntos
Xantinas/história , Xantinas/uso terapêutico , História do Século XX , História do Século XXI , Humanos , Estudos Retrospectivos , Xantinas/química
10.
Food Res Int ; 114: 20-29, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30361017

RESUMO

Cocoa shell (CS) is a co-product of the cocoa industry used mainly as fuel for boilers but with secondary applications as fertilizer and in animal feed. Although it is known that this material is rich in flavanols and alkaloids, to date, a study has not been conducted that has quantitatively identified these compounds in CS. Thus, the aim of this work was to characterize CS in terms of its composition, regarding catechin, epicatechin, procyanidin B2, caffeine and theobromine, and to evaluate the extraction kinetics of the total flavanols using pressurized liquid extraction (PLE) with absolute ethanol. For the determination of the extraction kinetic data, the DMAC method was used, while each compound was quantified using a UPLC-MS/MS analysis. The major compounds found were theobromine and epicatechin (mean values of 9.89 and 3.5 mg/g CS, respectively). PLE proved to be quite effective; the flavanols extraction yield was enhanced by increasing the temperature and extraction time however, high extraction times and temperatures degraded the procyanidins B2. Peleg's model applied to extraction data description provided a reasonable agreement with the experimental results, which allows their application in modeling and optimization of solid-liquid extraction of the total flavanols from cocoa bean shell.


Assuntos
Antioxidantes/isolamento & purificação , Cacau/química , Flavonoides/isolamento & purificação , Extração Líquido-Líquido/métodos , Sementes/química , Xantinas/isolamento & purificação , Antioxidantes/análise , Antioxidantes/química , Cromatografia Líquida de Alta Pressão , Etanol/química , Flavonoides/análise , Flavonoides/química , Resíduos Industriais , Cinética , Espectrometria de Massas em Tandem , Termogravimetria , Xantinas/análise , Xantinas/química
11.
Molecules ; 23(9)2018 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-30200192

RESUMO

Based on in silico results, recently we have assumed that FSCPX, an irreversible A1 adenosine receptor antagonist, inhibits the action of NBTI that is apparent on E/c curves of adenosine receptor agonists. As a mechanism for this unexpected effect, we hypothesized that FSCPX might modify the equilibrative and NBTI-sensitive nucleoside transporter (ENT1) in a way that allows ENT1 to transport adenosine but impedes NBTI to inhibit this transport. This assumption implies that our method developed to estimate receptor reserve for agonists with short half-life such as adenosine, in its original form, overestimates the receptor reserve. In this study, therefore, our goals were to experimentally test our assumption on this effect of FSCPX, to improve our receptor reserve-estimating method and then to compare the original and improved forms of this method. Thus, we improved our method and assessed the receptor reserve for the direct negative inotropic effect of adenosine with both forms of this method in guinea pig atria. We have found that FSCPX inhibits the effects of NBTI that are mediated by increasing the interstitial concentration of adenosine of endogenous (but not exogenous) origin. As a mechanism for this action of FSCPX, inhibition of enzymes participating in the interstitial adenosine production can be hypothesized, while modification of ENT1 can be excluded. Furthermore, we have shown that, in comparison with the improved form, the original version of our method overestimates receptor reserve but only to a small extent. Nevertheless, use of the improved form is recommended in the future.


Assuntos
Antagonistas do Receptor A1 de Adenosina/farmacologia , Adenosina/metabolismo , Átrios do Coração/efeitos dos fármacos , Átrios do Coração/metabolismo , Receptor A1 de Adenosina/metabolismo , Tioinosina/análogos & derivados , Xantinas/farmacologia , Antagonistas do Receptor A1 de Adenosina/química , Animais , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Cobaias , Tioinosina/farmacologia , Xantinas/química
12.
Electrophoresis ; 39(19): 2446-2453, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30051931

RESUMO

Discovering hit compounds and optimization processes in medicinal chemistry nowadays could be improved by predictive tools, based on the relationship between structure of molecules and lipophilic properties. Lipophilicity of drug candidate can affect both the pharmacokinetic and pharmacodynamics properties, in particular, the ability of a molecule to cross the cell membrane. Among the new methods for determination of the lipophilicity of compounds, micellar electrokinetic chromatography (MEKC) is considered to be an appropriate one for bioactive molecules, as it closely mimics the physiological conditions. In this paper MEKC was used for the estimation of the lipophilicity of 24 derivatives of 8-alkoxy-7H-purine-2,6-dione, designed and synthesized as potential antidepressant/anxiolytic and antipsychotic agents. The results of experimental method were compared with calculated in silico parameters (AlogPs and milogP by Virtual Computational Laboratory website, log PPallas by Pallas 3.1, Mlog P by Marvin, log PChemS by ChemSketch, log PChemDraw by ChemBioUltra) using Principal Component Analysis (PCA) method. Finally, using estimated log P values for selected compounds ligand - lipophilicity efficiency (LLE), per cent efficiency index (PEI), and binding efficiency index (BEI) parameters were calculated. Applied MEKC procedure could be used for selection of potential lead structure in a group of 7H-purine-2,6-dione derivatives.


Assuntos
Cromatografia Capilar Eletrocinética Micelar/métodos , Psicotrópicos/química , Xantinas/química , Descoberta de Drogas , Interações Hidrofóbicas e Hidrofílicas , Ligantes , Modelos Lineares , Psicotrópicos/análise , Psicotrópicos/farmacocinética , Xantinas/análise , Xantinas/farmacocinética
13.
J Microbiol Biotechnol ; 28(7): 1147-1155, 2018 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-29926702

RESUMO

The degradation efficiency and catabolism pathways of the different methylxanthines (MXs) in isolated caffeine-tolerant strain Pseudomonas putida CT25 were comprehensively studied. The results showed that the degradation efficiency of various MXs varied with the number and position of the methyl groups on the molecule (i.e., xanthine > 7-methylxanthine ≈ theobromine > caffeine > theophylline > 1-methylxanthine). Multiple MX catabolism pathways coexisted in strain CT25, and a different pathway would be triggered by various MXs. Demethylation dominated in the degradation of N-7-methylated MXs (such as 7-methylxanthine, theobromine, and caffeine), where C-8 oxidation was the major pathway in the catabolism of 1-methylxanthine, whereas demethylation and C-8 oxidation are likely both involved in the degradation of theophylline. Enzymes responsible for MX degradation were located inside the cell. Both cell culture and cell-free enzyme assays revealed that N-1 demethylation might be a rate-limiting step for the catabolism of the MXs. Surprisingly, accumulation of uric acid was observed in a cell-free reaction system, which might be attributed to the lack of activity of uricase, a cytochrome c-coupled membrane integral enzyme.


Assuntos
Cafeína/metabolismo , Redes e Vias Metabólicas , Pseudomonas putida/isolamento & purificação , Pseudomonas putida/metabolismo , Microbiologia do Solo , Xantinas/metabolismo , Biodegradação Ambiental , Cafeína/química , Tolerância a Medicamentos , Jardins , Pseudomonas putida/enzimologia , Pseudomonas putida/crescimento & desenvolvimento , Solo , Especificidade por Substrato , Chá/microbiologia , Teobromina/química , Teobromina/metabolismo , Teofilina/química , Teofilina/metabolismo , Ácido Úrico/metabolismo , Xantina/química , Xantina/metabolismo , Xantinas/química
14.
Mini Rev Med Chem ; 18(14): 1168-1174, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29692248

RESUMO

In the past decades, many efforts were undertaken to develop ligands for the adenosine receptors, with the purpose to individuate agonists and antagonists affinity and selectivity for each subtypes, namely A1, A2A, A2B, and A3. These intense studies allowed a deeper knowledge of the nature and, moreover, of the pathophysiological roles of all the adenosine receptor subtypes. In particular, the involvement of the A2A adenosine receptor subtype in some physiological mechanisms in the brain, that could be related to important diseases such as the Parkinson's disease, encouraged the research in this field. Particular attention was given to the antagonists endowed with high affinity and selectivity since they could have a real employment in the treatment of Parkinson's disease, and some compounds, such as istradefylline, preladenant and tozadenant, are already studied in clinical trials. Actually, the role of A2A antagonists in Parkinson's disease is becoming contradictory due to contrasting results in the last studies, but, at the same time, new possible employments are emerging for this class of antagonists in cancer pathologies as much interesting to legitimate further efforts in the research of A2A ligands.


Assuntos
Antagonistas do Receptor A2 de Adenosina/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Receptor A2A de Adenosina/metabolismo , Antagonistas do Receptor A2 de Adenosina/química , Compostos Bicíclicos com Pontes/química , Compostos Bicíclicos com Pontes/metabolismo , Compostos Bicíclicos com Pontes/uso terapêutico , Cafeína/química , Cafeína/metabolismo , Cafeína/uso terapêutico , Dopaminérgicos/química , Dopaminérgicos/metabolismo , Dopaminérgicos/uso terapêutico , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Doença de Parkinson/patologia , Receptor A2A de Adenosina/química , Xantinas/química , Xantinas/metabolismo , Xantinas/uso terapêutico
15.
Planta Med ; 84(12-13): 839-844, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29539647

RESUMO

Cocoa and chocolate, prepared from cocoa beans that originate from the fruits of the cocoa tree Theobroma cacao, have a long-standing reputation as healthy food, including mood-enhancing effects. In spite of many clinical trials with chocolate, cocoa, or its constituents, the mechanisms of action on mood and cognition remain unclear. More in particular, it is still controversial which constituents may contribute to the psychopharmacological activities, ranging from the major cacao flavanols and methylxanthines to the minor amines, amides, and alkaloids. In this review a critical appraisal is made of recent studies on mood and cognition, with a special emphasis on analytical characterization of the test samples. It is concluded that the mood and cognition-enhancing effects of cocoa and chocolate can be ranked from more general activities associated with flavanols and methylxanthines, to more specific activities related to minor constituents such as salsolinol, with on top the orosensory properties of chocolate. Therefore, the "mood pyramid" of cocoa and chocolate is proposed as a new concept. To understand the role and interactions of the different major and minor constituents of cocoa, it is recommended that all test samples used in future in vitro, in vivo, or human studies should be phytochemically characterized in much more detail than is common practice today.


Assuntos
Afeto/efeitos dos fármacos , Cacau/química , Chocolate/análise , Cognição/efeitos dos fármacos , Flavonoides/farmacologia , Xantinas/farmacologia , Flavonoides/química , Humanos , Xantinas/química
16.
Carbohydr Polym ; 182: 21-28, 2018 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-29279117

RESUMO

Alkali treatment of lignocellulosic biomass is conducted to remove hemi-cellulose and lignin, further increasing the reactivity and accessibility of cellulose. Ultrasound-assisted xanthation of alkali cellulose is optimized by response surface methodology (RSM) with a Box-Behnken design. A predicting mathematical model is obtained by fitting experimental data, and it is verified by analysis of variance. Response surface plots and the contour plots obtained from the model are applied to determine the interactions of experimental variables. The optimum conditions are NaOH concentration 1.3mol/L, ultrasonic time 71.6min and CS2 dosage 1.5mL. FTIR, SEM and XPS characterizations confirm the synthesis and sorption mechanism of cellulose xanthate (CX). Biosorption of Pb (II) onto CX obeys pseudo-second order model and Langmuir model. The sorption mechanism is attributed to surface complexation or ion exchange. CX shows good reusability for Pb (II) sorption. The maximum sorption capacity of Pb(II) is 134.41mg/g, higher than that of other biosorbents. CX has great potential as an efficient and low-cost biosorbent for wastewater treatment.


Assuntos
Celulose/análogos & derivados , Celulose/química , Chumbo/química , Ondas Ultrassônicas , Xantinas/química , Adsorção , Biomassa , Propriedades de Superfície
17.
J Inorg Biochem ; 181: 104-110, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29150325

RESUMO

Ilex paraguariensis, yerba mate is a native plant from the southern region of Brazil. Studies showed that yerba mate has an antioxidant potential, which could help to reduce the risk of developing neurodegenerative diseases, as Alzheimer's Disease (AD). It's known that I. paraguariensis grows in acid soils with aluminium (Al), which is bioavailable in these soils. Al has a neurotoxic potential related with the progression of neurological disorders. This study aim was to evaluate the potential of I. paraguariensis in the etiology of AD using strains of Caenorhabditis elegans and the concentration of Al and antioxidants in the yerba mate extract. The results of the I. paraguariensis infusions made at 65°C and at 75° C show that there was no significant difference between both temperatures when preparing the tea infusion in relation to the presence of Al, methylxanthines, phenolic compounds and flavonoids. Additionally, in the case of Al, there was no difference between the extracts prepared at both temperatures. The behavioral parameters of C. elegans were altered after a long-term exposure to both factors: I. paraguariensis extract and Al. Through the antioxidant levels results along with the Al content on the Acetylcholinesterase (AChE) activity it is possible to observe that the acute and chronic exposure to Al and I. paraguariensis leaves extract are very similar to wild-type worms. Moreover, we can observe that the results in both the transgenic strains long-term exposed to I. paraguariensis leaves extract and to the Al concentrations presented an increase in the AChE activity.


Assuntos
Alumínio/toxicidade , Doença de Alzheimer/etiologia , Modelos Animais de Doenças , Contaminação de Alimentos , Ilex paraguariensis/química , Poluentes do Solo/toxicidade , Chás de Ervas/efeitos adversos , Acetilcolinesterase/química , Acetilcolinesterase/metabolismo , Alumínio/análise , Doença de Alzheimer/prevenção & controle , Animais , Animais Geneticamente Modificados , Antioxidantes/análise , Antioxidantes/uso terapêutico , Comportamento Animal/efeitos dos fármacos , Brasil , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/agonistas , Proteínas de Caenorhabditis elegans/metabolismo , Flavonoides/análise , Flavonoides/uso terapêutico , Ilex paraguariensis/crescimento & desenvolvimento , Síndromes Neurotóxicas/fisiopatologia , Fenóis/análise , Fenóis/uso terapêutico , Folhas de Planta/química , Folhas de Planta/crescimento & desenvolvimento , Poluentes do Solo/análise , Chás de Ervas/análise , Testes de Toxicidade Aguda , Testes de Toxicidade Crônica , Xantinas/análise , Xantinas/química , Xantinas/uso terapêutico
18.
Zygote ; 25(6): 719-730, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29179786

RESUMO

We produced a new chemical compound based on methylxanthines and polyphenols (CCMP) present in the chemical matrix of guaraná (Paullinia cupana), a seed extract with antioxidant properties. After supplementation with the standard extract of resveratrol, a well documented antioxidant found in other plant sources, we investigated whether this resveratrol-enriched compound could improve sperm viability and modulate differentially reactive oxygen species (ROS) and nitric oxide (NO) levels in thawed sperm. Sperm samples obtained from healthy young donors were treated with different concentrations of guaraná extract (0.1, 1, 5 or 10 mg/ml) and cells were frozen at -80°C for 24 h. In addition, the potential protective effects of guaraná treatment on sperm treated with pro-oxidant compound (200 µM hydrogen peroxide, H2O2) were assessed. Samples were also exposed to three concentrations of CCMP before being frozen in liquid nitrogen (-196°C) or in an ultrafreezer (-80°C) for 24 h, and both pre-freezing and post-thaw measurements of viability and oxidative stress were performed. Guaraná supplementation at 10 mg/ml significantly increased post-thaw viability and decreased oxidative metabolism of the sperm. Moreover, selected concentrations of CCMP improved viability and oxidative metabolism in sperm samples pre-freezing. Furthermore, CCMP showed cryoprotective activity by increasing viability and decreasing oxidative stress in post-thaw samples. In summary, these findings suggested that CCMP supplementation acts as a cryoprotectant to modulate ROS and NO levels in thawed sperm. CCMP could be used to enhance sperm quality and reproductive success.


Assuntos
Óxido Nítrico/metabolismo , Paullinia/química , Extratos Vegetais/farmacologia , Polifenóis/química , Motilidade Espermática/efeitos dos fármacos , Espermatozoides/fisiologia , Xantinas/química , Adulto , Antioxidantes/farmacologia , Crioprotetores/farmacologia , Congelamento , Humanos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Análise do Sêmen , Espermatozoides/efeitos dos fármacos , Adulto Jovem
19.
Molecules ; 22(11)2017 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-29125553

RESUMO

The four receptors that signal for adenosine, A1, A2A, A2B and A3 ARs, belong to the superfamily of G protein-coupled receptors (GPCRs). They mediate a number of (patho)physiological functions and have attracted the interest of the biopharmaceutical sector for decades as potential drug targets. The many crystal structures of the A2A, and lately the A1 ARs, allow for the use of advanced computational, structure-based ligand design methodologies. Over the last decade, we have assessed the efficient synthesis of novel ligands specifically addressed to each of the four ARs. We herein review and update the results of this program with particular focus on molecular dynamics (MD) and free energy perturbation (FEP) protocols. The first in silico mutagenesis on the A1AR here reported allows understanding the specificity and high affinity of the xanthine-antagonist 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX). On the A2AAR, we demonstrate how FEP simulations can distinguish the conformational selectivity of a recent series of partial agonists. These novel results are complemented with the revision of the first series of enantiospecific antagonists on the A2BAR, and the use of FEP as a tool for bioisosteric design on the A3AR.


Assuntos
Receptores Purinérgicos P1/química , Ligantes , Simulação de Dinâmica Molecular , Mutação/genética , Antagonistas de Receptores Purinérgicos P1/química , Estereoisomerismo , Termodinâmica , Xantinas/química
20.
Future Med Chem ; 9(15): 1731-1747, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28871831

RESUMO

AIM: The discovery of new bronchodilators with higher efficacy than theophylline is an important issue for asthmatic patients. MATERIALS & METHODS: Theophylline 2, 8-bromotheophylline 4 and theobromine 6 were reacted with different 2/3-chloro-N-phenylacetamides 1a-d or their propanamide analogs 1e-g to obtain 3a-g, 5a-g and 7a-g, respectively. The target compounds were screened for their in vitro bronchodilator activity using isolated guinea pig tracheal rings precontracted with histamine and compared with their precursors. RESULTS: Many compounds exhibited promising activity especially 3d, 3f, 5d, 7d and 7e. 2D-QSAR study resulted in a significant model (N = 24, n = 5, R 2 = 0.848, R 2cvOO = 0.748, R 2cvMO = 0.745, F = 21.215, s 2 = 0.0002) using CODESSA-Pro software. CONCLUSION: These compounds can be considered as promising hits for potent bronchodilators that may be useful for further investigations. [Formula: see text].


Assuntos
Broncodilatadores/química , Broncodilatadores/farmacologia , Xantinas/química , Animais , Broncoconstrição/efeitos dos fármacos , Broncodilatadores/síntese química , Cobaias , Histamina/toxicidade , Concentração Inibidora 50 , Relação Quantitativa Estrutura-Atividade , Traqueia/efeitos dos fármacos , Traqueia/fisiologia , Xantinas/síntese química , Xantinas/farmacologia
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