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1.
Top Curr Chem (Cham) ; 378(1): 11, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31903506

RESUMO

The dramatic increase in atmospheric carbon dioxide (CO2) concentrations has attracted human attention and many strategies about converting CO2 into high-value chemicals have been put forward. Metal-organic frameworks (MOFs), as a class of versatile materials, have been widely used in CO2 capture and chemical conversion, due to their unique porosity, multiple active centers and good stability and recyclability. Herein, we focused on the processes of chemical conversion of CO2 by MOFs-based catalysts, including the coupling reactions of epoxides, aziridines or alkyne molecules, CO2 hydrogenation, and other CO2 conversion reactions. The synthesized methods and high catalytic activity of MOFs-based materials were also analyzed systematically. Finally, a brief perspective on feasible strategies is presented to improve the catalytic activity of novel MOFs-based materials and explore the new CO2 conversion reactions.


Assuntos
Dióxido de Carbono/química , Estruturas Metalorgânicas/química , Alcenos/química , Aminas/química , Aziridinas/química , Catálise , Compostos de Epóxi/química , Hidrogenação , Líquidos Iônicos/química
2.
Zhongguo Zhong Yao Za Zhi ; 44(21): 4566-4572, 2019 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-31872649

RESUMO

Nowadays,the advantages of traditional Chinese medicine(TCM) for treatment of tumors are increasingly prominent.Triptolide shows wide-spectrum and highly effective anti-tumor activity. Moreover,nano-carrier-based triptolide drug delivery system is more powerful in improving water solubility and pharmacokinetic behavior of the drug,but it is easy to cause toxic and side effects that should not be neglected on human body. Because of tumor vascular heterogeneity and PEGylation dilemma,nanoparticulate drug delivery systems need to overcome multiple physiological and pathological barriers from drug administration to functioning. It is difficult for traditional triptolide nanoparticulate drug delivery systems to achieve active accumulation of nano-drug in tumor tissues and specific drug release in tumor target site solely relying on enhanced permeability and retention effect of solid tumor,limiting their application and clinical transformation in treatment of tumors. Based on the traditional nano-preparation system,the new functionalized nano-drug delivery system further enhances the nano-drug enrichment,penetration and controlled release at the tumor sites,which is of great significance in improving bioavailability,anti-tumor efficacy and reducing the side effects of drugs. In this paper,we summarized and analyzed the researches on new triptolide functionalized nano-drug delivery system from four perspectives,including tumor active targeting,tumor microenvironment response,polymer-drug conjugates,and multidrug co-delivery for tumor treatment,expecting to provide ideas for in-depth research and clinical application of triptolide and some other active anti-tumor TCM ingredients.


Assuntos
Diterpenos/química , Sistemas de Liberação de Medicamentos , Nanopartículas , Fenantrenos/química , Compostos de Epóxi/química , Humanos
3.
J Agric Food Chem ; 67(36): 10174-10184, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31418563

RESUMO

The progress of lipid oxidation in foods is evaluated by measuring the peroxides and their scission products. However, hydrogen abstraction-independent pathways are not considered by commonly applied methods despite the known reactivity of epoxides toward biomolecules. Herein, a novel liquid chromatography tandem-mass spectrometry method was developed to detect hydroperoxidized and epoxidized triacylglycerols (TAGs) without derivatization or hydrolyzation of food samples. Epoxidized TAGs could be detected in refined canola oil at concentrations of 96.8 ± 2.08 µM, while only 5.77 ± 0.04 µM hydroperoxidized TAGs could be determined. In contrast to canola oil, margarine was more resistant to lipid oxidation since generation of epoxidized TAGs could only be marginally enhanced from 21.7 ± 0.48 to 28.8 ± 0.64 µM in margarine after treatment at 180 °C for 60 min, as also reflected by a peroxide value of 0.80 ± 0.00 mequiv O2/kg, which remained unchanged. The new method allows the assessment of food safety by the simultaneous measurement of hydroperoxidized and epoxidized TAGs without hydrolysis and laborious sample preparation.


Assuntos
Cromatografia Líquida/métodos , Margarina/análise , Espectrometria de Massas/métodos , Óleo de Brassica napus/química , Triglicerídeos/química , Compostos de Epóxi/química , Peróxido de Hidrogênio/química , Oxirredução
4.
Chem Biol Interact ; 312: 108797, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31422076

RESUMO

Epidemiological studies of 1,3-butadiene (BD) exposures have reported a possible association with chronic myelogenous leukemia (CML), which is defined by the presence of the t(9;22) translocation (Philadelphia chromosome) creating an oncogenic BCR-ABL fusion gene. Butadiene diepoxide (DEB), the most mutagenic of three epoxides resulting from BD, forms DNA-DNA crosslink adducts that can lead to DNA double-strand breaks (DSBs). Thus, a study was designed to determine if (±)-DEB exposure of HL60 cells, a promyelocytic leukemia cell line lacking the Philadelphia chromosome, can produce t(9;22) translocations. In HL60 cells exposed for 3 h to 0-10 µM DEB, overlapping dose-response curves suggested a direct relationship between 1,4-bis-(guan-7-yl)-2,3-butanediol crosslink adduct formation (R = 0.977, P = 0.03) and cytotoxicity (R = 0.961, P = 0.002). Experiments to define the relationships between cytotoxicity and the induction of micronuclei (MN), a dosimeter of DNA DSBs, showed that 24 h exposures of HL60 cells to 0-5.0 µM DEB caused significant positive correlations between the concentration and (i) the degree of cytotoxicity (R = 0.998, p = 0.002) and (ii) the frequency of MN (R = 0.984, p = 0.016) at 48 h post exposure. To determine the relative induction of MN and t(9;22) translocations following exposures to DEB, or x-rays as a positive control for formation of t(9;22) translocations, HL60 cells were exposed for 24 h to 0, 1, 2.5, or 5 µM DEB or to 0, 2.0, 3.5, or 5.0 Gy x-rays, or treatments demonstrated to yield 0, 20%, 50%, or 80% cytotoxicity. Treatments between 0 and 3.5 Gy x-rays caused significant dose-related increases in both MN (p < 0.001) and t(9;22) translocations (p = 0.01), whereas DEB exposures causing similar cytotoxicity levels did not increase translocations over background. These data indicate that, while DEB induces DNA DSBs required for formation of MN and translocations, acute DEB exposures of HL60 cells did not produce the Philadelphia chromosome obligatory for CML.


Assuntos
Adutos de DNA/metabolismo , Compostos de Epóxi/toxicidade , Translocação Genética/efeitos dos fármacos , Butadienos/metabolismo , Adutos de DNA/análise , Compostos de Epóxi/química , Células HL-60 , Humanos , Radiação Ionizante , Translocação Genética/efeitos da radiação
5.
J Agric Food Chem ; 67(33): 9220-9231, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31347838

RESUMO

Slow-release fungicide formulations (azoxystrobin, epoxiconazole, and tebuconazole) shaped as pellets and granules in a matrix of biodegradable poly(3-hydroxybutyrate) and natural fillers (clay, wood flour, and peat) were constructed. Infrared spectroscopy showed no formation of chemical bonds between components in the experimental formulations. The formulations of pesticides had antifungal activity against Fusarium verticillioides in vitro. A study of biodegradation of the experimental fungicide formulations in the soil showed that the degradation process was mainly influenced by the type of formulation without significant influence of the type of filler. More active destruction of the granules led to a more rapid accumulation of fungicides in the soil. The content of fungicides present in the soil as a result of degradation of the formulations and fungicide release was determined by their solubility. Thus, all formulations are able to function in the soil for a long time, ensuring gradual and sustained delivery of fungicides.


Assuntos
Argila/química , Preparações de Ação Retardada/química , Composição de Medicamentos/métodos , Fungicidas Industriais/química , Hidroxibutiratos/química , Poliésteres/química , Solo/química , Madeira/química , Preparações de Ação Retardada/farmacologia , Portadores de Fármacos/química , Composição de Medicamentos/instrumentação , Compostos de Epóxi/química , Compostos de Epóxi/farmacologia , Fungicidas Industriais/farmacologia , Fusarium/efeitos dos fármacos , Cinética , Pirimidinas/química , Pirimidinas/farmacologia , Estrobilurinas/química , Estrobilurinas/farmacologia , Triazóis/química , Triazóis/farmacologia
6.
J Chromatogr A ; 1603: 269-277, 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31279475

RESUMO

In this study, a hydroxypropyl-ß-cyclodextrin (HP-ß-CD) functionalized monolithic capillary column was prepared by one-pot sequential reaction for the first time. The preparation of the HP-ß-CD functionalized monolithic column involves two sequential reactions in one pot: (1) the ring opening reaction between HP-ß-CD and glycidyl methacrylate (GMA) catalyzed by 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU); (2) the copolymerization of GMA-HP-ß-CD, ethylene dimethacrylate (EDMA) and 2-acrylamido-2-methyl propane sulfonic acid (AMPS). A series of monolithic columns were successfully prepared by varying the temperature of the ring opening reaction or several copolymerization parameters (the type and composition of porogenic solvents, ratio of GMA-HP-ß-CD to EDMA and polymerization temperature). Then, the morphologies and structures of the resulting monolithic stationary phases were characterized by optical microscopy, scanning electron microscopy (SEM) and nitrogen adsorption analysis. Raman spectroscopy clearly indicated the successful bonding of HP-ß-CD onto the monolith. When the prepared chiral stationary phase (CSP) was applied for the separation of a set of racemic compounds by capillary electrochromatography (CEC), including racemic anticholinergic drugs, ß-adrenergic drugs, meptazinol and its intermediates, satisfactory separation selectivities were obtained. Additionally, the column also showed excellent separation abilities towards four flavanone glycosides epimers. Furthermore, the prepared monolithic columns exhibited satisfactory stability and reproducibilities of retention time, resolution and column efficiency. These results demonstrated the potential and usefulness of the developed one-pot sequential strategy in the preparation of other derivatized CD functionalized monolithic columns.


Assuntos
2-Hidroxipropil-beta-Ciclodextrina/química , Eletrocromatografia Capilar/métodos , Adsorção , Compostos de Epóxi/química , Metacrilatos/química , Nitrogênio/química , Permeabilidade , Polimerização , Polímeros/química , Espectroscopia de Prótons por Ressonância Magnética , Reprodutibilidade dos Testes , Análise Espectral Raman , Estereoisomerismo , Temperatura Ambiente
7.
Eur J Med Chem ; 176: 378-392, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31121546

RESUMO

In the past decades, triptolide has attracted considerable interests in the organic and medicinal chemistry society owing to its intriguing structure features and promising multiple pharmacological activities. However, its limited water solubility and oral bioavailability, imprecise mechanism of action and sever toxicity, scares from nature and difficulty in the synthesis have greatly hindered its clinical potential. Hence, to circumvent such problems, a lot of elegant total synthesis have been developed. With the advancement of the total synthesis, various triptolide derivatives have been synthesized and tested in the search for more drug-like derivatives for potential anticancer agents, anti-inflammatory agents, immunosuppressive agents and anti-Alzheimer's agents, etc. Meanwhile, through designing and synthesizing of various of bioactive probes, some molecular targets that are responsible for the multiple pharmacology activities as well as toxicity of triptolide have been identified. It is no doubt will help the future development of new drug-like triptolide derivatives. In order to gain a comprehensive and deep understanding of the area and provides suggestions for triptolide's further studies, i) the medicinal chemistry advancement, ii) bioactive probes-based cellular target identification and iii) clinical progress of triptolide derivatives are reviewed in this article.


Assuntos
Diterpenos/química , Diterpenos/farmacologia , Fenantrenos/química , Fenantrenos/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Química Farmacêutica/métodos , Ensaios Clínicos como Assunto , Compostos de Epóxi/química , Compostos de Epóxi/farmacologia , Humanos , Imunossupressores/química , Imunossupressores/farmacologia , Estrutura Molecular , Relação Estrutura-Atividade
8.
J Chem Ecol ; 45(5-6): 464-473, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31111291

RESUMO

Different enantiomers of chiral compounds within floral perfumes usually trigger distinct responses in insects; however, this has frequently been neglected in studies investigating semiochemicals in plant-pollinator interactions. Approximately 1000 neotropical plants produce floral perfumes as the only reward for pollinators, i.e. male euglossine bees. The chiral compound carvone epoxide is a key component of the scent bouquet of many perfume-rewarding plants that are pollinated by males of Eulaema. Here, we tested the biological activity of the four carvone epoxide stereoisomers to four Eulaema species occurring in the Atlantic Rainforest of NE-Brazil. We determined the stereochemistry of carvone epoxide in the floral scent of several Catasetum species, tested whether the antennae of bees respond differentially to these stereoisomers and investigated if there is a behavioural preference for any of the stereoisomers. We found that 1) Catasetum species emit only the (-)-trans-stereoisomer of carvone epoxide, 2) for E. atleticana and E. niveofasciata antennal responses to the (-)-trans-carvone epoxide were significantly stronger than those to (-)-cis-carvone epoxide, 3) the strength and pattern of antennal responses to all 4 stereoisomers (separately tested) did not differ among Eulaema species, and 4) there were significant differences in attractiveness of the four stereoisomers to the bees species with the (-)-trans-stereoisomer being particularly attractive. We assume (-)-trans-carvone epoxide to be the dominant isomer in perfume-rewarding plants pollinated by Eulaema. The universal occurrence of carvone epoxide in Catasetum species pollinated by Eulaema, suggests that this compound has evolved in perfume-rewarding as a specific attractant for Eulaema bees as pollinators.


Assuntos
Abelhas/fisiologia , Monoterpenos/química , Animais , Comportamento Animal/efeitos dos fármacos , Cromatografia Gasosa , Compostos de Epóxi/química , Flores/química , Flores/metabolismo , Masculino , Monoterpenos/farmacologia , Orchidaceae/química , Orchidaceae/metabolismo , Estereoisomerismo
9.
Chem Commun (Camb) ; 55(45): 6361-6364, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31062010

RESUMO

A simple technique for the preparation of [18F]HF has been developed and applied to the generation of an [18F]FeF species for opening sterically hindered epoxides. This method has been successfully employed to prepare four drug-like molecules, including 5-[18F]fluoro-6-hydroxy-cholesterol, a potential adrenal/endocrine PET imaging agent. This easily automated one-pot procedure produces sterically hindered fluorohydrin PET imaging agents in good yields and high molar activities.


Assuntos
Compostos de Epóxi/química , Fluoretos/química , Hidrocarbonetos Fluorados/química , Ferro/química , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/química , Radioisótopos de Flúor , Hidrocarbonetos Fluorados/síntese química
10.
Chem Pharm Bull (Tokyo) ; 67(8): 864-871, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31142691

RESUMO

Lung cancer is one of the most common malignant cancers in the world. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is a second- or third-line therapy for mutated non-small cell lung cancer (NSCLC). It usually becomes drug resistance after a period of treatment. Triptolide (TPL) is an epoxy diterpenoid lactone compound extracted from Tripterygium wilfordii HOOK. F. and many studies demonstrated that TPL has a synergistic effect when combined with chemotherapy drugs. In this research, we plan to evaluate the combined effect of TPL and EGFR-TKIs (Gefitinib, Erlotinib, and Icotinib) and investigate the possible mechanisms. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was conducted to detect the cell viabilities, combined effect was evaluated by Combination Index. Molecular docking study was used to predict the binding ability of TPL. The expression of proteins was detected by Western blot. MTT results showed TPL had synergistic effect with three EGFR-TKIs at different concentrations on H1975 cells but not on H1299 cells. Molecular docking study demonstrated that TPL with T790M/L858R EGFR can form a more stable compound than that with wild type EGFR. Western blot results showed TPL inhibited the EGFR/Akt pathway and increased the expression of Bax and the ratio of Bax and Bcl-2 in H1975 cells. In conclusion, TPL had synergistic effect with three EGFR-TKIs on H1975 cells but not on H1299 cells, which may be due to the binding ability of TPL and different-type EGFR. The synergistic effect of TPL on H1975 cells may be partly related to the inhibition of the EGFR/Akt pathway.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Diterpenos/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Fenantrenos/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Diterpenos/síntese química , Diterpenos/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Compostos de Epóxi/síntese química , Compostos de Epóxi/química , Compostos de Epóxi/farmacologia , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Simulação de Acoplamento Molecular , Estrutura Molecular , Fenantrenos/síntese química , Fenantrenos/química , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/metabolismo , Relação Estrutura-Atividade
11.
Am J Chin Med ; 47(4): 769-785, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31091976

RESUMO

Tripterygium wilfordii Hook F. (TWHF), a traditional Chinese medicine, has been widely used to treat autoimmune and inflammatory diseases including rheumatoid arthritis, systemic lupus erythematosus and dermatomyositis in China. Recently, studies have demonstrated that the bioactive components of TWHF have effective therapeutic potential for neurodegenerative diseases including Alzheimer's disease, Parkinson's disease and Multiple Sclerosis. In this paper, we summarize the research progress of triptolide and celastrol (the two major TWHF components) as well as their analogues in the treatment of neurodegenerative diseases. In addition, we review and discuss the molecular mechanisms and structure features of those two bioactive TWHF components, highlighting their therapeutic promise in neurodegenerative diseases.


Assuntos
Diterpenos/uso terapêutico , Doenças Neurodegenerativas/tratamento farmacológico , Fenantrenos/uso terapêutico , Fitoterapia , Tripterygium/química , Triterpenos/uso terapêutico , Doença de Alzheimer/tratamento farmacológico , Animais , Diterpenos/química , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Compostos de Epóxi/química , Compostos de Epóxi/isolamento & purificação , Compostos de Epóxi/farmacologia , Compostos de Epóxi/uso terapêutico , Humanos , Medicina Tradicional Chinesa , Conformação Molecular , Fármacos Neuroprotetores , Doença de Parkinson/tratamento farmacológico , Fenantrenos/química , Fenantrenos/isolamento & purificação , Fenantrenos/farmacologia , Triterpenos/química , Triterpenos/isolamento & purificação , Triterpenos/farmacologia
12.
Talanta ; 200: 387-397, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31036200

RESUMO

A label-free immunosensor for the determination of Cadherin-like protein 22 (CDH 22) was successfully developed by using poly(thiophene-g-glycidyl methacrylate) (PT-GMA) brush type polymer modified disposable ITO electrode. This immunosensor was fabricated by immobilizing of anti-CDH 22 antibodies on epoxy functional groups of brush type polymer. Brush type polymer was coated on the disposable ITO electrode by utilizing the spin-coating method. Electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV) analyses were employed for monitoring of electrochemical properties of the immunosensor. Single frequency impedance (SFI) analysis was utilized to investigate the specific recognition interaction between anti-CDH22 antibody and CDH22 antigen. Fourier-transform infrared spectroscopy (FTIR) and Raman spectroscopy were used to prove the attachment of anti-CDH 22 antibodies on the electrode surface. Atomic force microscopy (AFM) and Scanning electron microscopy (SEM) analyses were carried out to indicate the changes formed on the sensing interface during the immobilization process. The electrochemical signals in response to different concentrations of CDH 22 antigens were evaluated with EIS measurements under the optimal experimental conditions. With the increase of concentrations of CDH 22 antigens, a thick protein layer was obtained on the electrode surface, resulting in higher electrochemical signals. The variations in impedance values were proportional to the CDH22 concentrations, with a wide linear detection range of 0.01-3 pg/mL, and a low detection limit of 3.2 fg/mL. The suggested immunosensor was an easy and low-cost label-free detection technique and provided a simple way for determination of cancer biomarkers such as CDH 22.


Assuntos
Caderinas/sangue , Técnicas Eletroquímicas , Imunoensaio/instrumentação , Imunoensaio/métodos , Polímeros/química , Compostos de Estanho/química , Biomarcadores/sangue , Eletrodos , Compostos de Epóxi/química , Humanos , Metacrilatos/química , Estrutura Molecular , Tamanho da Partícula , Polímeros/síntese química , Propriedades de Superfície , Tiofenos/química
13.
Dalton Trans ; 48(23): 8106-8115, 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31017170

RESUMO

The syntheses of oxidorhenium(v) complexes [ReOCl(L1a-c)2] (3a-c), equipped with the bidentate, mono-anionic phenol-dimethyloxazoline ligands HL1a-c are described. Ligands HL1b-c contain functional groups on the phenol ring, compared to parent ligand 2-(4,4-dimethyl-4,5-dihydro-1,3-oxazol-2-yl)-phenol H1a; namely a methoxy group ortho to the hydroxyl position (2-(4,4-dimethyl-4,5-dihydro-1,3-oxazol-2-yl)-6-methoxyphenol, H1b), or a nitro group para to the hydroxyl position (2-(4,4-dimethyl-4,5-dihydro-1,3-oxazol-2-yl)-4-nitrophenol, H1c). Furthermore, oxidorhenate(v) complexes (NBu4)[ReOCl3(L1a-b)] (2a-b) were synthesized for solid state structural comparisons to 3a-b. All novel complexes are fully characterized including NMR, IR and UV-Vis spectroscopy, MS spectrometry, X-ray crystallography, elemental analysis as well as cyclic voltammetry. The influence of functional groups (R = -H, -OMe and -NO2) on the catalytic activity of 3a-c was investigated in two benchmark catalytic reactions, namely cyclooctene epoxidation and perchlorate reduction. In addition, the previously described oxidorhenium(v) complex [ReOCl(oz)2] (4), employing the phenol-oxazoline ligand 2-(4,5-dihydro-2-oxazolyl)phenol Hoz, was included in these catalysis studies. Complex 4 is a rare case in oxidorhenium(v) chemistry where two stereoisomers could be separated and fully characterized. With respect to the position of the oxazoline nitrogen atoms on the rhenium atom, these two stereoisomers are referred to as N,N-cis and N,N-trans isomer. A potential correlation between spectroscopic and structural data to catalytic activity was evaluated.


Assuntos
Compostos Organometálicos/química , Rênio/química , Catálise , Eletroquímica , Compostos de Epóxi/química , Modelos Moleculares , Conformação Molecular , Percloratos/química , Estereoisomerismo
14.
Environ Sci Pollut Res Int ; 26(17): 17535-17547, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31025280

RESUMO

Epoxiconazole (EPX) is a triazole fungicide commonly used in agriculture and for domestic purposes around the world. The excessive application of this pesticide may result in a variety of adverse effects on non-target organisms, including humans. Since, the liver and kidneys are the target organs of this fungicide, potential hepatotoxic and nephrotoxic effects are of high relevance. Thus, our study aimed to investigate the toxic effects of EPX on the liver and kidney of Wistar rats. The exposure of rats to EPX at these concentrations (8, 24, 40, 56 mg/kg bw representing, respectively, NOEL (no observed effect level), NOEL × 3, NOEL × 5, and NOEL × 7) for 28 days significantly enhances hepatic and renal lipid peroxidation which is accompanied by an increase in the level of protein oxidation. Furthermore, the results of the present study clearly indicated that EPX administration induces an increase in the levels of DNA damage in a dose-dependent manner. In addition, the activities of liver and kidney antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione S-transferase (GST) are increased significantly in EPX-treated rats at concentrations of 8, 24, and 40 mg/kg bw. However, with the dose NOEL × 7 (56 mg/kg bw of EPX), the activities of CAT, GPx, and GST are decreased. Indeed, EPX-intoxicated rats revealed a significant reduction in acetylcholinesterase (AChE) activity in both liver and kidney compared with the control group. Also, our results demonstrated that the EPX administration leads to a disruption of the hepatic (aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH)) and renal (uric acid and creatinine) functions. The biochemical perturbations obtained in the present study are corroborated with the histopathological modifications. Since EPX treatment caused severe damage in the overall histo-architecture of liver and kidney tissues, these results suggest that administration of EPX induced a marked deregulation of liver and kidney functions. Graphical abstract.


Assuntos
Alanina Transaminase/metabolismo , Antioxidantes/metabolismo , Aspartato Aminotransferases/metabolismo , Catalase/metabolismo , Dano ao DNA/efeitos dos fármacos , Compostos de Epóxi/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa Transferase/metabolismo , Rim/efeitos dos fármacos , L-Lactato Desidrogenase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Triazóis/metabolismo , Alanina Transaminase/química , Animais , Aspartato Aminotransferases/química , Catalase/química , Compostos de Epóxi/química , Glutationa Peroxidase/química , Glutationa Transferase/química , L-Lactato Desidrogenase/química , Masculino , Oxirredução , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , Triazóis/química
15.
Molecules ; 24(9)2019 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-31027338

RESUMO

The substitution of toxic precursors such as bisphenol A by renewable and safer molecules has become a major challenge. To overcome this challenge, the 12 principles of green chemistry should be taken into account in the development of future sustainable chemicals and processes. In this context, this paper reports the highly efficient synthesis of oligo-isosorbide glycidyl ethers from bio-based starting materials by a rapid one-pot heterogeneous ultrasound-assisted synthesis. It was demonstrated that the use of high-power ultrasound in solvent-free conditions with sodium hydroxide microbeads led for the first time to a fully epoxidated prepolymer with excellent epoxy equivalent weight (EEW). The structure of the epoxy precursor was characterized by FT-IR, NMR spectroscopy and high-resolution mass spectrometry (HRMS). The efficiency of the ultrasound-assisted synthesis was attributed to the physical effects caused by micro-jets on the surface of the solid sodium hydroxide microspheres following the asymmetrical collapse of cavitation bubbles.


Assuntos
Técnicas de Química Sintética , Compostos de Epóxi/química , Isossorbida/química , Ondas Ultrassônicas , Compostos de Epóxi/síntese química , Química Verde , Isossorbida/síntese química , Estrutura Molecular , Análise Espectral
16.
Trends Pharmacol Sci ; 40(5): 327-341, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30975442

RESUMO

Triptolide, a compound isolated from a Chinese medicinal herb, possesses potent antitumor, immunosuppressive, and anti-inflammatory properties, but is clinically limited due to its poor solubility, bioavailability, and toxicity. Recently, Minnelide, a water-soluble prodrug of triptolide, was shown to have potent antitumor activity in various preclinical cancer models. Minnelide is currently in Phase II clinical trials for treatment of advanced pancreatic cancer, which has fueled increased interest in this promising agent. Here, we review the recent advances in the biological activity of triptolide and its analogs, their mechanisms of actions, and their clinical developments. A special emphasis is given to proteins and pathways within the tumor and stromal compartments that are targeted by triptolide and its analogs as well as the ongoing clinical trials.


Assuntos
Antineoplásicos/farmacologia , Diterpenos/química , Diterpenos/farmacologia , Fenantrenos/farmacologia , Animais , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Diterpenos/uso terapêutico , Compostos de Epóxi/química , Compostos de Epóxi/farmacologia , Compostos de Epóxi/uso terapêutico , Humanos , Imunossupressores/química , Imunossupressores/farmacologia , Imunossupressores/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Fenantrenos/química , Fenantrenos/uso terapêutico
17.
Org Lett ; 21(8): 2615-2619, 2019 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-30969776

RESUMO

Hydroxy-containing cyclic ethers react with thermally generated benzynes to produce aryl ethers. Diverse reactivity was observed. Cleavage of the cyclic ether was involved in most of the pathways. The transformations are rationalized via initial formation of oxonium ion-containing 1,3-zwitterions arising from preferential nucleophilic attack on the benzyne by the ether oxygen. Pinacol-like rearrangements, including ring expansion, to yield aldehydes or ketones and oxirane fragmentations to generate aryl enol ethers were main competing events.


Assuntos
Derivados de Benzeno/química , Compostos de Epóxi/química , Óxido de Etileno/química , Glicóis/química , Propanóis/química , Álcoois/química , Aldeídos/química , Cicloexenos/química , Éteres Cíclicos/química , Cetonas/química
18.
Int J Mol Sci ; 20(8)2019 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-31003413

RESUMO

Gamma-ray radiation was used as a clean and easy method for turning the physicochemical properties of graphene oxide (GO) in this study. Silane functionalized-GO were synthesized by chemically grafting 3-aminopropyltriethoxysilane (APTES) and 3-glycidyloxypropyltrimethoxysilane (GPTES) onto GO surface using gamma-ray irradiation. This established non-contact process is used to create a reductive medium which is deemed simpler, purer and less harmful compared conventional chemical reduction. The resulting functionalized-GO were characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), thermogravimetric analysis (TGA), and Raman spectroscopy. The chemical interaction of silane with the GO surface was confirmed by FT-IR. X-ray diffraction reveals the change in the crystalline phases was due to surface functionalization. Surface defects of the GO due to the introduction of silane mioties was revealed by Raman spectroscopy. Thermogravimetric analysis of the functionalized-GO exhibits a multiple peaks in the temperature range of 200-650 °C which corresponds to the degradation of chemically grafted silane on the GO surface.


Assuntos
Grafite/química , Compostos de Organossilício/química , Propilaminas/química , Silanos/química , Compostos de Epóxi/síntese química , Compostos de Epóxi/química , Compostos de Epóxi/efeitos da radiação , Raios gama , Grafite/síntese química , Grafite/efeitos da radiação , Microscopia Eletrônica de Varredura , Compostos de Organossilício/efeitos da radiação , Propilaminas/síntese química , Propilaminas/efeitos da radiação , Silanos/síntese química , Silanos/efeitos da radiação , Espectroscopia de Infravermelho com Transformada de Fourier , Análise Espectral Raman , Propriedades de Superfície/efeitos da radiação , Temperatura Ambiente , Termogravimetria , Difração de Raios X
19.
Talanta ; 198: 464-471, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30876588

RESUMO

Prodrug treosulfan undergoes a pH and temperature-dependent activation to the monoepoxide intermediate (EBDM) and (2S,3S)-1,2:3,4-diepoxybutane (DEB). The latter DNA cross-linker is presently believed to mainly account for the pharmacological action of treosulfan. However, neither respective monoadducts nor cross-links have been isolated from treosulfan-treated DNA, and the exact alkylation mechanism of the treosulfan epoxides is unclear. In this paper, liquid chromatography method with tandem mass spectrometry detection (LC-MS/MS) for simultaneous determination of the N-7-guanine adducts of EBDM and DEB - (2'S,3'S)-N-7-(2'3'-dihydroxy-4'-methylsulfonyloxybut-1'-yl)guanine (HMSBG), N-7-(2',3',4'-trihydroxybut-1'-yl)guanine (THBG), and 1,4-bis(N-7-guanyl)butane-2,3-diol cross-link (bis-N7G-BD) - in calf-thymus DNA has been developed and validated for the first time. The mixture of drug-free nucleic acid with the analytes and 15N-isotope labeled internal standards underwent a mild acid thermal hydrolysis and ultrafiltration (cut-off 10 kDa). Following offline LC purification, the analytes and internal standards were determined in the LC-MS/MS system with an electrospray interface. Complete resolution of THBG, HMSBG, and bis-N7G-BD was accomplished on a Zorbax Eclipse C18 column using gradient elution with a mobile phase composed of 0.1% formic acid and acetonitrile. Calibration curves were linear in the ranges: THBG 0.2-200 pmol, HMSBG 0.2-20 pmol, and bis-N7G-BD 0.4-40 pmol. The limits of quantitation allowed to determine the adducts at concentration of 330 or 660 per 109 DNA nucleotides. The LC-MS/MS method was adequately precise (coefficient of variation ≤ 16.7%) and accurate (relative error ≤ 17.7%). Calibration standards were stable for 14 days at -25 °C. The validated method enabled determination of THBG, HMSBG, and bis-N7G-BD in calf thymus DNA treated with treosulfan at pH 7.2 and 37 °C, which constitutes a novel bioanalytical application. To the authors' best knowledge, the quantification of THBG and bis-N7G-BD in one analytical run is also reported for the first time.


Assuntos
Bussulfano/análogos & derivados , Adutos de DNA/análise , DNA/química , Compostos de Epóxi/química , Guanina/análise , Pró-Fármacos/química , Bussulfano/química , Cromatografia Líquida , Guanina/análogos & derivados , Concentração de Íons de Hidrogênio , Conformação Molecular , Espectrometria de Massas em Tandem , Temperatura Ambiente
20.
Methods Mol Biol ; 1972: 25-39, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30847782

RESUMO

In the last few years, biopharmaceuticals-therapeutic drugs which are generally obtained by using molecular biology techniques-have become a major growing sector in pharmaceutical industry. A large part of these biopharmaceuticals are therapeutic glycoproteins. The production of these drugs and their purification process are implying the development of efficient analytical methods, which allow quick and reliable control of the manufacturing process and ensuring the regulatory compliance about the quality of these drugs. Capillary gel electrophoresis (CGE) in the presence of sodium dodecyl sulfate (SDS) is becoming a method of choice in the quality control of these biopharmaceuticals. On the other hand, CGE can be improved if analyses are carried out in microchip format.This chapter reports a detailed microchips gel electrophoresis (MGE) method to separate glycosylated and deglycosylated forms of α1-acid glycoprotein (AGP) labeled with Chromeo P540, using SU-8 microchips and laser induced fluorescence detection. Due to the analogy between AGP and some therapeutic glycoproteins, we have selected AGP as a model system to illustrate the potential of MGE in the analysis of this type of biopharmaceutical compounds.


Assuntos
Eletroforese em Microchip/métodos , Compostos de Epóxi/química , Lasers , Orosomucoide/análise , Polímeros/química , Fluorescência , Glicosilação , Processamento de Imagem Assistida por Computador , Espectrometria de Massas , Peso Molecular , Padrões de Referência
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