RESUMO
Aim: This study aimed to enhance the aqueous dissolution of SRPK inhibitor N-(2-(piperidin-1-yl)-5-(trifluoromethyl)phenyl)isonicotinamide (SRPIN340).Materials & Methods: A complex with p-sulfonic calix[6]arene (Host) and SRPIN340 (Guest) was prepared, studied via 1H nuclear magnetic resonance (NMR) and theoretical calculations and biologically evaluated on cancer cell lines.Results & conclusion: The 1:1 host (H)/guest (G) complex significantly enhanced the aqueous dissolution of SRPIN340, achieving 64.8% water solubility as determined by 1H NMR quantification analysis. The H/G complex reduced cell viability by 75% for HL60, â¼50% for Nalm6 and Jurkat, and â¼30% for B16F10 cells. It exhibited greater cytotoxicity than free SRPIN340 against Jurkat and B16F10 cells. Theoretical studies indicated hydrogen bond stabilization of the complex, suggesting broader applicability of SRPIN340 across diverse biological systems.
[Box: see text].
Assuntos
Antineoplásicos , Calixarenos , Sobrevivência Celular , Calixarenos/química , Calixarenos/farmacologia , Humanos , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Sobrevivência Celular/efeitos dos fármacos , Fenóis/química , Fenóis/farmacologia , Camundongos , Espectroscopia de Ressonância Magnética , Animais , Ácidos Sulfônicos/química , Ácidos Sulfônicos/antagonistas & inibidores , Ácidos Sulfônicos/farmacologia , Linhagem Celular Tumoral , Estrutura Molecular , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/síntese química , Proliferação de Células/efeitos dos fármacos , Piperidinas/química , Piperidinas/farmacologiaRESUMO
This work aimed to evaluate the physicochemical changes during the roasting process of Robusta and Arabica coffee. The highest content of total phenolics was detected in roasted coffee at temperatures of 135 °C/20.20 min, 210 °C/9.02 min, 210 °C/11.01 min, and 220 °C/13.47 min for both species. Robusta coffee showed greater antioxidant activity compared to Arabica coffee, except for the profiles at 230 °C/17.43 min and 275 °C/7.46 min that did not differ between samples by the DPPH and FRAP methods. For Arabica coffee, the antioxidant activity was independent of the roasting profile used. Robusta coffee presented higher values of the indexes b* (intensity of yellow vs blue), c* (chroma) and hue, being characterized as lighter and with greater chroma and hue. The highest levels of caffeoylquinic acid (5-CQA) were observed in Robusta coffee. Arabica coffee had lower trigonelline values. Caffeic acid and hydroxymethylfurfural were identified only in Robusta coffee. However, the results provided solid knowledge for the design of general properties and chemical compounds generated from binomials of roasting time and temperature that are little used in the world market.
RESUMO
ABSTRACT: The effects of gamma irradiation and pasteurization on the stability of anthocyanins and antioxidant capacity during storage of jussara pulp were investigated. Jussara pulp was divided into 6 portions: control (no treatment), irradiated pulp (2, 4, 6, 8 kGy) and pasteurized pulp (92 ºC/ 1 minute). Portions were stored at 4ºC for 60 days. The phenolic extract was prepared with a solution of methanol/water/formic acid. The following analyses were performed every 15 days: contents of total phenolic compounds by Folin-Ciocauteau, cyanidin-3-glycoside and cyanidin-3-rutiniside by HPLC and antioxidant capacity (ABTS and DPPH). Total phenolics and anthocyanins decreased with the increasing irradiation dose and storage time. Pasteurization did not affect the phenolic concentration immediately after processing. However, the contents of TPC and cyanidin-3-rutiniside were reduced during storage of the pasteurized pulp. No processed samples presented characteristics similar to the control at the end of storage.
RESUMO: Os efeitos da radiação gama e pasteurização na estabilidade das antocianinas e na capacidade antioxidante durante o armazenamento da polpa de jussara foram avaliados. A polpa de jussara foi dividida em diferentes tratamentos: controle (sem tratamento), polpa irradiada (2, 4, 6, 8 kGy) e pasteurizada polpa (92 ºC / 1 minuto). Os tratamentos foram armazenados a 4ºC por 60 dias. O extrato fenólico foi preparado com uma solução de metanol / água / ácido fórmico. As seguintes análises foram realizadas a cada 15 dias: teores de compostos fenólicos totais por Folin-Ciocauteau, cianidina 51 3-glicosídeo e cianidina-3-rutinisida por HPLC e capacidade antioxidante (ABTS e DPPH). Os fenólicos totais e as antocianinas diminuíram com o aumento da dose de irradiação e do tempo de armazenamento. A pasteurização não afetou a concentração fenólica imediatamente após o processamento. No entanto, os teores de TPC e cianidina-3-rutinisida foram reduzidos durante o armazenamento da polpa pasteurizada. Nenhuma amostra processada apresentou características semelhantes ao controle ao final do armazenamento.
RESUMO
The effects of gamma irradiation and pasteurization on the stability of anthocyanins and antioxidant capacity during storage of jussara pulp were investigated. Jussara pulp was divided into 6 portions: control (no treatment), irradiated pulp (2, 4, 6, 8 kGy) and pasteurized pulp (92 ºC/ 1 minute). Portions were stored at 4ºC for 60 days. The phenolic extract was prepared with a solution of methanol/water/formic acid. The following analyses were performed every 15 days: contents of total phenolic compounds by Folin-Ciocauteau, cyanidin-3-glycoside and cyanidin-3-rutiniside by HPLC and antioxidant capacity (ABTS and DPPH). Total phenolics and anthocyanins decreased with the increasing irradiation dose and storage time. Pasteurization did not affect the phenolic concentration immediately after processing. However, the contents of TPC and cyanidin-3-rutiniside were reduced during storage of the pasteurized pulp. No processed samples presented characteristics similar to the control at the end of storage.
Os efeitos da radiação gama e pasteurização na estabilidade das antocianinas e na capacidade antioxidante durante o armazenamento da polpa de jussara foram avaliados. A polpa de jussara foi dividida em diferentes tratamentos: controle (sem tratamento), polpa irradiada (2, 4, 6, 8 kGy) e pasteurizada polpa (92 ºC / 1 minuto). Os tratamentos foram armazenados a 4ºC por 60 dias. O extrato fenólico foi preparado com uma solução de metanol / água / ácido fórmico. As seguintes análises foram realizadas a cada 15 dias: teores de compostos fenólicos totais por Folin-Ciocauteau, cianidina 51 3-glicosídeo e cianidina-3-rutinisida por HPLC e capacidade antioxidante (ABTS e DPPH). Os fenólicos totais e as antocianinas diminuíram com o aumento da dose de irradiação e do tempo de armazenamento. A pasteurização não afetou a concentração fenólica imediatamente após o processamento. No entanto, os teores de TPC e cianidina-3-rutinisida foram reduzidos durante o armazenamento da polpa pasteurizada. Nenhuma amostra processada apresentou características semelhantes ao controle ao final do armazenamento.
Assuntos
Pasteurização , Euterpe/efeitos da radiação , Antocianinas/efeitos da radiação , AntioxidantesRESUMO
Teak wood has chemical compounds that can be used for pharmaceutical and textile industries, in addition, this compounds are related to resistance to biodeterioration, color and modification processes. Heartwood and sapwood of T. grandis (teak), 15 years-old, were characterized by Py-CG/MS analysis and syringyl (S)/guaiacyl (G) ratio was evaluated. Heartwood and sapwood were pyrolyzed at 550 °C and 62 and 51 compounds were identified from them, respectively. The acetic acid (10%) and levoglucosan (26.65%) were the most abundant compound in the sapwood and heartwood, respectively. The high acetic acid content enhances the use of teak wood to production of artificial essences for perfumery, paints, dyes. While levoglucosan can be used in the manufacture of epoxy resins, antiparasitic and insecticides. The organic compounds identified include 2-methylanthraquinone as one of the main component responsible for the resistance of the teak wood to biological factors (fungi and termites). The syringyl (S)/guaiacyl (G) ratio of heartwood and sapwood was 0.51 and 0.50, respectively.
Assuntos
Lamiaceae , Lamiaceae/química , Madeira/química , FungosRESUMO
Ketoconazole (KTZ) is an antifungal agent; however, its bioavailability and therapeutic efficacy are reduced by the low aqueous solubility of the drug. Aiming at providing to improve the biopharmaceutical properties of KTZ, we studied the water-soluble different calix[n]arenes as carrier systems for KTZ. All calix[n]arene-KTZ tested showed in vitro antifungal activity superior or similar to free KTZ against Candida spp. The CX6Na/KTZ obtained by physical mixture and freeze-drying methods were the most active, decreasing KTZ concentrations required for growth inhibition against azole-resistant isolates (e.g., C. auris). Moreover, CX6Na/KTZ showed no toxic effect on Galleria mellonella larvae and the treatment of infected larvae with C. albicans and C. auris was effective at a lower dose compared with free KTZ. Thus, CX6Na/KTZ may have a potential approach to treat mycosis, especially by improvement of KTZ inhibitory activity against azole-resistant Candida.
Assuntos
Antifúngicos , Cetoconazol , Antifúngicos/farmacologia , Azóis/farmacologia , Candida , Candida albicans , Cetoconazol/farmacologia , Testes de Sensibilidade MicrobianaRESUMO
In this work, we describe for the first time the synthesis of a thiocarbazone for the selective determination of Cu2+ in distilled beverages. The method was based on the complexation reaction of Cu2+ with the thiocarbazone, and the colored product was analyzed using a smartphone application. The thiocarbazone reacts with Cu2+ to form a 1:1 (metal:ligand) complex. The Cu2+ complex was characterized by UV, IR and NMR spectral analyses. The proposed reaction yields a yellow color, and therefore, channel B of the RGB system was used in the analysis. After optimizing the reaction conditions, an analytical curve was obtained to determine Cu2+ concentrations ranging between 0.25 and 6.75 mg L-1; the use of 400 µL sample volumes led to a relative standard deviation (n = 5) of 3.2% and a detection limit of 0.18 mg L-1. Recovery experiments were performed with sugar cane spirits, whiskies and tequilas to evaluate the accuracy of the method, and the recovery obtained ranged from 80.5 to 112.2%.
Assuntos
Complexos de Coordenação , Saccharum , Bebidas Alcoólicas/análise , Bebidas , Cobre/análise , Grão Comestível/químicaRESUMO
Levoglucosan (LGA) is a promising chemical platform derived from the pyrolysis of biomass that offers access to a variety of value-added products. We report an efficient route to produce LGA via the pretreatment of biomass with niobium compounds (oxalate, chloride and oxide) followed by fast pyrolysis coupled with gas chromatography-mass spectrometry (Py-GC-MS) at temperatures of 350-600 °C. Catalytic pretreatment reduces the quantity of lignin in the biomass, concentrates the cellulose and enhance LGA formation during fast pyrolysis. The pretreatment also removes alkaline metals, preventing competitive side reactions. The effect of several parameters such as catalyst weight, time, temperature, and solvent, with the optimal pretreatment conditions determined to be 3 (wt.%) niobium oxalate for 1 h at 23 °C in water. Pretreatment increased the LGA yields by 6.40-fold for sugarcane bagasse, 4.15-fold for elephant grass, 4.13-fold for rice husk, 2.86-fold for coffee husk, and 1.86-fold for coconut husk as compared to the raw biomasses. These results indicate that biomass pretreatment using niobium derivates prior fast pyrolysis can be a promising technique for biomass thermochemical conversion in LGA and others important pyrolytic products.
Assuntos
Nióbio , Pirólise , Biomassa , Glucose/análogos & derivados , Temperatura Alta , LigninaRESUMO
The use of star anise oil from a natural source as a dienophile in the multicomponent double Povarov reaction (MCPRs) to produce highly substituted julolidines with diverse technological applications is described. Within the framework of green chemistry, these MCPRs have many advantages such as (i) use of water in the reaction, (ii) creation of up to six bonds in one sequence, (iii) water as a sole waste, (iv) 100% of carbon economy, (v) a metal-free process, and (vi) nontoxic and reusable organocatalysts. These advantages, along with a simple workup procedure, make this protocol greener for the synthesis of julolidines.
RESUMO
A new one-pot cascade reaction-based application of Povarov reactions with a p-sulfonic acid calix[4]arene catalyst for the synthesis of a series of 34 julolidine derivatives with substituents at C8 or C9 in good to excellent yields is reported. These microwave-assisted reactions proceeded efficiently, had short reaction times, were metal-free, were low cost, and used an inexpensive, easily available and nontoxic catalyst. These advantages, along with a simple workup procedure, make this protocol a very efficient and green alternative to the traditional methods for constructing these types of N-heterocyclic skeletons. In addition, this protocol allows the formation of julolidine structures, which requires the construction of four new C-C bonds and two C-N bonds. A mechanism for the Povarov reaction involving a stepwise sequence via ionic intermediates was proposed and validated.
RESUMO
An efficient method for the synthesis of quinolines using microwave irradiation was developed providing 28 quinolines with good yields. The reaction procedures are environmentally friendly, convenient, mild and of easy work-up. Quinolines were evaluated for their antifungal, anticancer and antioxidant properties and exhibited high activities in all tests performed.
Assuntos
Antifúngicos/farmacologia , Sequestradores de Radicais Livres/farmacologia , Micro-Ondas , Quinolinas/farmacologia , Antifúngicos/síntese química , Antifúngicos/química , Candida albicans/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Cryptococcus neoformans/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Sequestradores de Radicais Livres/síntese química , Sequestradores de Radicais Livres/química , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Quinolinas/síntese química , Quinolinas/química , Relação Estrutura-AtividadeRESUMO
Baccharis dracunculifolia DC (common name "alecrim-do-campo" in Brazil) is a plant with widespread distribution in South America that is the botanical origin of green propolis. The aim of this study was to evaluate the chemical composition and acaricidal activity of the essential oil of B. dracunculifolia and its constituents nerolidol and limonene on unengorged larvae and engorged females of Rhipicephalus microplus (Acari: Ixodidae). The essential oil yield was 0.8% of dry mass and the major constituents were nerolidol (22.3%), germacrene D (7.2%), limonene (6.9%), ß-pinene (6.7) and bicyclogermacrene (6.5%). The acaricidal activity of the essential oil and the pure compounds nerolidol and (R)-(+)-limonene were assessed in the laboratory through the modified larval packet test (LPT) and the female immersion test (FIT). In the LPT, the essential oil and nerolidol were both active, causing more than 90% mortality at concentrations from 15.0 and 10.0 mg mL(-1), respectively, whereas (R)-(+)-limonene was not active. In the FIT, the oil and nerolidol caused reduction in the quantity and quality of eggs produced, with control percentages of 96.3% and 90.3% at concentrations of 60.0 and 50.0 mg mL(-1), respectively. It can be concluded that the essential oil obtained from the aerial parts of B. dracunculifolia and its major component nerolidol have high activity on R. microplus larvae and engorged females.
Assuntos
Acaricidas/farmacologia , Baccharis/química , Óleos Voláteis/farmacologia , Óleos de Plantas/farmacologia , Rhipicephalus/efeitos dos fármacos , Acaricidas/química , Acaricidas/isolamento & purificação , Animais , Cicloexenos/química , Cicloexenos/isolamento & purificação , Cicloexenos/farmacologia , Feminino , Larva/efeitos dos fármacos , Limoneno , Óleos Voláteis/química , Óleos Voláteis/isolamento & purificação , Óleos de Plantas/química , Óleos de Plantas/isolamento & purificação , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/farmacologia , Terpenos/química , Terpenos/isolamento & purificação , Terpenos/farmacologiaRESUMO
A diastereoselective three-component cascade reaction, catalyzed by p-sulfonic acid calix[4]arene, provides a unique method to access diverse julolidine derivatives in high yields. Additionally, the reaction was also monitored by mass spectrometry and the mechanistic pathway uncovered.
RESUMO
Yacon flour has been considered a food with prebiotic potential because of the high levels of fructooligosaccharides, which allows for its use in formulating synbiotic foods. The purpose of this study was to evaluate the effect of yacon flour and probiotic (Bifidobacterium longum) on the modulation of variables related to bone health. Thirty-two Wistar rats were divided into 4 groups: control, yacon flour, diet+B. longum, and yacon flour+B. longum. After euthanasia, the bones were removed for analysis of biomechanical properties (thickness, length, and strength of fracture) and mineral content (Ca, Mg, and P); the cecum was removed for analysis of the microbiota and short-chain fatty acids. Tibia Ca, P, and Mg content was significantly (P<.05) higher in groups fed diet+B. longum, yacon flour+B. longum than in the control group. An increase in fracture strength was observed in the yacon flour (8.1%), diet+B. longum (8.6%), and yacon flour+B. longum (14.6%) in comparison to the control group. Total anaerobe and weight of the cecum were higher (P<.05) in rats consuming the yacon flour diet compared with the other groups. Cecal concentration of propionate was higher in all experimental groups compared with the control (P<.05). Yacon flour in combination with B. longum helped increase the concentration of minerals in bones, an important factor in the prevention of diseases such as osteoporosis.
Assuntos
Asteraceae/química , Bifidobacterium , Densidade Óssea/efeitos dos fármacos , Preparações de Plantas/farmacologia , Simbióticos , Tíbia/efeitos dos fármacos , Animais , Cálcio/metabolismo , Ceco/anatomia & histologia , Ceco/metabolismo , Ceco/microbiologia , Fraturas Ósseas/prevenção & controle , Frutose/farmacologia , Frutose/uso terapêutico , Magnésio/metabolismo , Masculino , Minerais/metabolismo , Oligossacarídeos/farmacologia , Oligossacarídeos/uso terapêutico , Tamanho do Órgão/efeitos dos fármacos , Osteoporose/prevenção & controle , Fósforo/metabolismo , Fitoterapia , Preparações de Plantas/uso terapêutico , Tubérculos , Prebióticos , Probióticos , Propionatos/metabolismo , Ratos , Ratos Wistar , Tíbia/anatomia & histologia , Tíbia/metabolismoRESUMO
This study focused on the use of NMR techniques as a tool for the investigation of complex formation between proparacaine and cyclodextrins (CDs) or p-sulfonic acid calix[6]arene. The pH dependence of the complexation of proparacaine with beta-CD and p-sulfonic acid calix[6]arene was studied and binding constants were determined by (1)H NMR spectroscopy [diffusion-ordered spectroscopy (DOSY)] for the charged and uncharged forms of the local anesthetic in beta-CD and p-sulfonic acid calix[6]arene. The stoichiometries of the complexes was determined and rotating frame Overhauser enhancement spectroscopy (ROESY) 1D experiments revealed details of the molecular insertion of proparacaine into the beta-CD and p-sulfonic acid calix[6]arene cavities. The results unambiguously demonstrate that pH is an important factor for the development of supramolecular architectures based on beta-CD and p-sulfonic acid calix[6]arene as the host molecules. Such host-guest complexes were investigated in view of their potential use as new therapeutic formulations, designed to increase the bioavailability and/or to decrease the systemic toxicity of proparacaine in anesthesia procedures.
Assuntos
Calixarenos/química , Fenóis/química , Propoxicaína/química , beta-Ciclodextrinas/química , Anestésicos Locais , Sítios de Ligação , Concentração de Íons de Hidrogênio , Espectroscopia de Ressonância Magnética/métodos , Ácidos Sulfônicos/químicaRESUMO
Calixarenes, macrocyclic compounds of phenolic units linked by methylene groups at the 2,6-positions, present some of the requirements to serve as platforms for the design and synthesis of biological active compounds. They are also interesting host molecules for chemical biology study purposes. Their basic molecular scaffold has potential ability for molecule recognition; it is promptly synthesized in large amounts, and might be easily modified for maximizing molecular interactions toward relevant guest molecules. Calixarenes present well-defined conformational properties and cavities with molecular dimensions that enable to encapsulate guest drugs. Calixarenes have been shown to have antiviral, antibacterial, antifungal, and anticancer activities (including HIV as target). We provide here an overview of the use of calixarenes either as new chemical entity of distinct biological activities or as host for bioactive guest molecules. The importance of calixarenes for drugs development is discussed. The use of Nuclear Magnetic Resonance (NMR) and Mass Spectrometry (MS) techniques for the study of calixarenes as biological molecule hosts is also described.
Assuntos
Calixarenos , Desenho de Fármacos , Calixarenos/síntese química , Calixarenos/química , Sistemas de Liberação de Medicamentos , Espectroscopia de Ressonância Magnética , Espectrometria de MassasRESUMO
The topologies of proparacaine (PPC) in beta-cyclodextrin (beta-CD), PPC in egg phosphatidylcholine (EPC) liposomes and PPC in beta-CD in EPC were investigated using NMR experiments (1D ROESY and saturation transfer difference (STD)). This is the first description of the STD technique applied to PPC-EPC-beta-CD system, revealing that not only PPC was imbedded in EPC bilayer, but beta-CD was also interacting with liposome vesicles. These results are novel and were rationalized as the spontaneous formation of a ternary complex with some beta-CD molecules bound to external liposome vesicles surfaces.
Assuntos
Lipossomos/química , Espectroscopia de Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética/normas , Propoxicaína/química , beta-Ciclodextrinas/química , Sítios de Ligação , Difusão , Estrutura Molecular , Padrões de ReferênciaRESUMO
'Non-covalent synthesis' of novel chiral hosts (calix[6]arene-chiral amine complexes) and its application to enantiomeric discrimination was investigated by (1)H NMR spectroscopy. The topology of a ternary complex was proposed for the calix[6]arene-amine-sulfoxide to rationalize the chiral recognition.
Assuntos
Técnicas Biossensoriais/métodos , Calixarenos/química , Espectroscopia de Ressonância Magnética/métodos , Fenóis/química , Aminas/química , Safrol/análogos & derivados , Safrol/química , EstereoisomerismoRESUMO
Theoretical calculations and the isomeric product composition for a series of eight meta-substituted allyl aryl ethers confirm the reliability of a new (1)H NMR methodology used to predict aromatic Claisen regioselectivity from ground-state conformational preference of the reactant allyloxy group. Frontier HOMO-LUMO intramolecular orbital interactions, a classical approach in predicting reactivity and selectivity for Claisen rearrangements of allyl vinyl ethers, is shown to fail to mimic transition-state orbital interactions for aromatic Claisen rearrangements of meta-substituted allyl aryl ethers. B3LYP/6-31G(d,p) calculations on reactants and transition states are shown, however, to correctly predict the outcome of such aromatic Claisen rearrangements from either the preferential reactant ground-state conformation (theoretical predictions that agree with the NMR measurements) or the less energetic transition state, or both.